Transcriptional diversity during lineage commitment of human blood progenitors
Identifieur interne : 001B78 ( Pmc/Curation ); précédent : 001B77; suivant : 001B79Transcriptional diversity during lineage commitment of human blood progenitors
Auteurs : Lu Chen [Royaume-Uni] ; Myrto Kostadima [Royaume-Uni] ; Joost H. A. Martens [Pays-Bas] ; Giovanni Canu [Royaume-Uni] ; Sara P. Garcia [Royaume-Uni] ; Ernest Turro [Royaume-Uni] ; Kate Downes [Royaume-Uni] ; Iain C. Macaulay [Royaume-Uni] ; Ewa Bielczyk-Maczynska [Royaume-Uni] ; Sophia Coe [Royaume-Uni] ; Samantha Farrow [Royaume-Uni] ; Pawan Poudel [Royaume-Uni] ; Frances Burden [Royaume-Uni] ; Sjoert B. G. Jansen [Royaume-Uni] ; William J. Astle [Royaume-Uni] ; Antony Attwood [Royaume-Uni] ; Tadbir Bariana [Royaume-Uni] ; Bernard De Bono [Royaume-Uni, Nouvelle-Zélande] ; Alessandra Breschi [Espagne] ; John C. Chambers [Royaume-Uni] ; Bridge Consortium ; Fizzah A. Choudry [Royaume-Uni] ; Laura Clarke [Royaume-Uni] ; Paul Coupland [Royaume-Uni] ; Martijn Van Der Ent [Pays-Bas] ; Wendy N. Erber [Australie] ; Joop H. Jansen [Pays-Bas] ; Rémi Favier [France] ; Matthew E. Fenech [Royaume-Uni] ; Nicola Foad [Royaume-Uni] ; Kathleen Freson [Belgique] ; Chris Van Geet [Belgique] ; Keith Gomez [Royaume-Uni] ; Roderic Guigo [Espagne] ; Daniel Hampshire [Royaume-Uni] ; Anne M. Kelly [Royaume-Uni] ; Hindrik H. D. Kerstens [Pays-Bas] ; Jaspal S. Kooner [Royaume-Uni] ; Michael Laffan [Royaume-Uni] ; Claire Lentaigne [Royaume-Uni] ; Charlotte Labalette [Royaume-Uni] ; Tiphaine Martin [Royaume-Uni] ; Stuart Meacham [Royaume-Uni] ; Andrew Mumford [Royaume-Uni] ; Sylvia Nürnberg [Royaume-Uni] ; Emilio Palumbo [Espagne] ; Bert A. Van Der Reijden [Pays-Bas] ; David Richardson [Royaume-Uni] ; Stephen J. Sammut [Royaume-Uni] ; Greg Slodkowicz [Royaume-Uni] ; Asif U. Tamuri [Royaume-Uni] ; Louella Vasquez [Royaume-Uni] ; Katrin Voss [Royaume-Uni] ; Stephen Watt [Royaume-Uni] ; Sarah Westbury [Royaume-Uni] ; Paul Flicek [Royaume-Uni] ; Remco Loos [Royaume-Uni] ; Nick Goldman [Royaume-Uni] ; Paul Bertone [Royaume-Uni, Allemagne] ; Randy J. Read [Royaume-Uni] ; Sylvia Richardson [Royaume-Uni] ; Ana Cvejic [Royaume-Uni] ; Nicole Soranzo [Royaume-Uni] ; Willem H. Ouwehand [Royaume-Uni] ; Hendrik G. Stunnenberg [Pays-Bas] ; Mattia Frontini [Royaume-Uni] ; Augusto Rendon [Royaume-Uni]Source :
- Science (New York, N.Y.) [ 0036-8075 ] ; 2014.
Abstract
Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identify extensive cell-type specific expression changes: 6,711 genes and 10,724 transcripts, enriched in non-protein coding elements at early stages of differentiation. In addition, we discovered 7,881 novel splice junctions and 2,301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrate experimentally cell specific isoform usage, identifying NFIB as a regulator of megakaryocyte maturation – the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.
Url:
DOI: 10.1126/science.1251033
PubMed: 25258084
PubMed Central: 4254742
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G." last="Jansen">Sjoert B. G. Jansen</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Astle, William J" sort="Astle, William J" uniqKey="Astle W" first="William J." last="Astle">William J. Astle</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Attwood, Antony" sort="Attwood, Antony" uniqKey="Attwood A" first="Antony" last="Attwood">Antony Attwood</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Bariana, Tadbir" sort="Bariana, Tadbir" uniqKey="Bariana T" first="Tadbir" last="Bariana">Tadbir Bariana</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Haematology, University College London Cancer Institute, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University College London Cancer Institute, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London</wicri:regionArea></affiliation></author><author><name sortKey="De Bono, Bernard" sort="De Bono, Bernard" uniqKey="De Bono B" first="Bernard" last="De Bono">Bernard De Bono</name><affiliation wicri:level="1"><nlm:aff id="A10">CHIME Institute, University College London, Archway Campus, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>CHIME Institute, University College London, Archway Campus, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Auckland Bioengineering Institute, University of Auckland, New Zealand</nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Auckland Bioengineering Institute, University of Auckland</wicri:regionArea></affiliation></author><author><name sortKey="Breschi, Alessandra" sort="Breschi, Alessandra" uniqKey="Breschi A" first="Alessandra" last="Breschi">Alessandra Breschi</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C." last="Chambers">John C. Chambers</name><affiliation wicri:level="1"><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial College Healthcare NHS Trust, DuCane Road, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ealing Hospital NHS Trust, Southall, Middlesex</wicri:regionArea></affiliation></author><author><name sortKey="Consortium, Bridge" sort="Consortium, Bridge" uniqKey="Consortium B" first="Bridge" last="Consortium">Bridge Consortium</name></author><author><name sortKey="Choudry, Fizzah A" sort="Choudry, Fizzah A" uniqKey="Choudry F" first="Fizzah A." last="Choudry">Fizzah A. Choudry</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Laura" sort="Clarke, Laura" uniqKey="Clarke L" first="Laura" last="Clarke">Laura Clarke</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Coupland, Paul" sort="Coupland, Paul" uniqKey="Coupland P" first="Paul" last="Coupland">Paul Coupland</name><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Ent, Martijn" sort="Van Der Ent, Martijn" uniqKey="Van Der Ent M" first="Martijn" last="Van Der Ent">Martijn Van Der Ent</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Erber, Wendy N" sort="Erber, Wendy N" uniqKey="Erber W" first="Wendy N." last="Erber">Wendy N. Erber</name><affiliation wicri:level="1"><nlm:aff id="A15">Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia</wicri:regionArea></affiliation></author><author><name sortKey="Jansen, Joop H" sort="Jansen, Joop H" uniqKey="Jansen J" first="Joop H." last="Jansen">Joop H. Jansen</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Favier, Remi" sort="Favier, Remi" uniqKey="Favier R" first="Rémi" last="Favier">Rémi Favier</name><affiliation wicri:level="1"><nlm:aff id="A17">Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif</wicri:regionArea></affiliation></author><author><name sortKey="Fenech, Matthew E" sort="Fenech, Matthew E" uniqKey="Fenech M" first="Matthew E." last="Fenech">Matthew E. Fenech</name><affiliation wicri:level="1"><nlm:aff id="A18">Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich</wicri:regionArea></affiliation></author><author><name sortKey="Foad, Nicola" sort="Foad, Nicola" uniqKey="Foad N" first="Nicola" last="Foad">Nicola Foad</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Freson, Kathleen" sort="Freson, Kathleen" uniqKey="Freson K" first="Kathleen" last="Freson">Kathleen Freson</name><affiliation wicri:level="1"><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Molecular and Vascular Biology, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Van Geet, Chris" sort="Van Geet, Chris" uniqKey="Van Geet C" first="Chris" last="Van Geet">Chris Van Geet</name><affiliation wicri:level="1"><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Molecular and Vascular Biology, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Gomez, Keith" sort="Gomez, Keith" uniqKey="Gomez K" first="Keith" last="Gomez">Keith Gomez</name><affiliation wicri:level="1"><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London</wicri:regionArea></affiliation></author><author><name sortKey="Guigo, Roderic" sort="Guigo, Roderic" uniqKey="Guigo R" first="Roderic" last="Guigo">Roderic Guigo</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Hampshire, Daniel" sort="Hampshire, Daniel" uniqKey="Hampshire D" first="Daniel" last="Hampshire">Daniel Hampshire</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kelly, Anne M" sort="Kelly, Anne M" uniqKey="Kelly A" first="Anne M." last="Kelly">Anne M. Kelly</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A20">Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kerstens, Hindrik H D" sort="Kerstens, Hindrik H D" uniqKey="Kerstens H" first="Hindrik H. D." last="Kerstens">Hindrik H. D. Kerstens</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S." last="Kooner">Jaspal S. Kooner</name><affiliation wicri:level="1"><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial College Healthcare NHS Trust, DuCane Road, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ealing Hospital NHS Trust, Southall, Middlesex</wicri:regionArea></affiliation></author><author><name sortKey="Laffan, Michael" sort="Laffan, Michael" uniqKey="Laffan M" first="Michael" last="Laffan">Michael Laffan</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Lentaigne, Claire" sort="Lentaigne, Claire" uniqKey="Lentaigne C" first="Claire" last="Lentaigne">Claire Lentaigne</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Labalette, Charlotte" sort="Labalette, Charlotte" uniqKey="Labalette C" first="Charlotte" last="Labalette">Charlotte Labalette</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Tiphaine" sort="Martin, Tiphaine" uniqKey="Martin T" first="Tiphaine" last="Martin">Tiphaine Martin</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A22">Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London</wicri:regionArea></affiliation></author><author><name sortKey="Meacham, Stuart" sort="Meacham, Stuart" uniqKey="Meacham S" first="Stuart" last="Meacham">Stuart Meacham</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Mumford, Andrew" sort="Mumford, Andrew" uniqKey="Mumford A" first="Andrew" last="Mumford">Andrew Mumford</name><affiliation wicri:level="1"><nlm:aff id="A23">School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Cellular and Molecular Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Nurnberg, Sylvia" sort="Nurnberg, Sylvia" uniqKey="Nurnberg S" first="Sylvia" last="Nürnberg">Sylvia Nürnberg</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Palumbo, Emilio" sort="Palumbo, Emilio" uniqKey="Palumbo E" first="Emilio" last="Palumbo">Emilio Palumbo</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Reijden, Bert A" sort="Van Der Reijden, Bert A" uniqKey="Van Der Reijden B" first="Bert A." last="Van Der Reijden">Bert A. Van Der Reijden</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Richardson, David" sort="Richardson, David" uniqKey="Richardson D" first="David" last="Richardson">David Richardson</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Sammut, Stephen J" sort="Sammut, Stephen J" uniqKey="Sammut S" first="Stephen J." last="Sammut">Stephen J. Sammut</name><affiliation wicri:level="1"><nlm:aff id="A24">Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A25">Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Slodkowicz, Greg" sort="Slodkowicz, Greg" uniqKey="Slodkowicz G" first="Greg" last="Slodkowicz">Greg Slodkowicz</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Tamuri, Asif U" sort="Tamuri, Asif U" uniqKey="Tamuri A" first="Asif U." last="Tamuri">Asif U. Tamuri</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Vasquez, Louella" sort="Vasquez, Louella" uniqKey="Vasquez L" first="Louella" last="Vasquez">Louella Vasquez</name><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Voss, Katrin" sort="Voss, Katrin" uniqKey="Voss K" first="Katrin" last="Voss">Katrin Voss</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Watt, Stephen" sort="Watt, Stephen" uniqKey="Watt S" first="Stephen" last="Watt">Stephen Watt</name><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Westbury, Sarah" sort="Westbury, Sarah" uniqKey="Westbury S" first="Sarah" last="Westbury">Sarah Westbury</name><affiliation wicri:level="1"><nlm:aff id="A26">School of Clinical Sciences, University of Bristol, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Clinical Sciences, University of Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Loos, Remco" sort="Loos, Remco" uniqKey="Loos R" first="Remco" last="Loos">Remco Loos</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Goldman, Nick" sort="Goldman, Nick" uniqKey="Goldman N" first="Nick" last="Goldman">Nick Goldman</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Bertone, Paul" sort="Bertone, Paul" uniqKey="Bertone P" first="Paul" last="Bertone">Paul Bertone</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A27">Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A28">Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Read, Randy J" sort="Read, Randy J" uniqKey="Read R" first="Randy J." last="Read">Randy J. Read</name><affiliation wicri:level="1"><nlm:aff id="A29">Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Richardson, Sylvia" sort="Richardson, Sylvia" uniqKey="Richardson S" first="Sylvia" last="Richardson">Sylvia Richardson</name><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Cvejic, Ana" sort="Cvejic, Ana" uniqKey="Cvejic A" first="Ana" last="Cvejic">Ana Cvejic</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Stunnenberg, Hendrik G" sort="Stunnenberg, Hendrik G" uniqKey="Stunnenberg H" first="Hendrik G." last="Stunnenberg">Hendrik G. Stunnenberg</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Frontini, Mattia" sort="Frontini, Mattia" uniqKey="Frontini M" first="Mattia" last="Frontini">Mattia Frontini</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Rendon, Augusto" sort="Rendon, Augusto" uniqKey="Rendon A" first="Augusto" last="Rendon">Augusto Rendon</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25258084</idno><idno type="pmc">4254742</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254742</idno><idno type="RBID">PMC:4254742</idno><idno type="doi">10.1126/science.1251033</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001D21</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D21</idno><idno type="wicri:Area/Pmc/Curation">001B78</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001B78</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transcriptional diversity during lineage commitment of human blood progenitors</title><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kostadima, Myrto" sort="Kostadima, Myrto" uniqKey="Kostadima M" first="Myrto" last="Kostadima">Myrto Kostadima</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Martens, Joost H A" sort="Martens, Joost H A" uniqKey="Martens J" first="Joost H. A." last="Martens">Joost H. A. Martens</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Canu, Giovanni" sort="Canu, Giovanni" uniqKey="Canu G" first="Giovanni" last="Canu">Giovanni Canu</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Garcia, Sara P" sort="Garcia, Sara P" uniqKey="Garcia S" first="Sara P." last="Garcia">Sara P. Garcia</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Turro, Ernest" sort="Turro, Ernest" uniqKey="Turro E" first="Ernest" last="Turro">Ernest Turro</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Downes, Kate" sort="Downes, Kate" uniqKey="Downes K" first="Kate" last="Downes">Kate Downes</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Macaulay, Iain C" sort="Macaulay, Iain C" uniqKey="Macaulay I" first="Iain C." last="Macaulay">Iain C. Macaulay</name><affiliation wicri:level="1"><nlm:aff id="A7">Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Bielczyk Maczynska, Ewa" sort="Bielczyk Maczynska, Ewa" uniqKey="Bielczyk Maczynska E" first="Ewa" last="Bielczyk-Maczynska">Ewa Bielczyk-Maczynska</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Coe, Sophia" sort="Coe, Sophia" uniqKey="Coe S" first="Sophia" last="Coe">Sophia Coe</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Farrow, Samantha" sort="Farrow, Samantha" uniqKey="Farrow S" first="Samantha" last="Farrow">Samantha Farrow</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Poudel, Pawan" sort="Poudel, Pawan" uniqKey="Poudel P" first="Pawan" last="Poudel">Pawan Poudel</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Burden, Frances" sort="Burden, Frances" uniqKey="Burden F" first="Frances" last="Burden">Frances Burden</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Jansen, Sjoert B G" sort="Jansen, Sjoert B G" uniqKey="Jansen S" first="Sjoert B. G." last="Jansen">Sjoert B. G. Jansen</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Astle, William J" sort="Astle, William J" uniqKey="Astle W" first="William J." last="Astle">William J. Astle</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Attwood, Antony" sort="Attwood, Antony" uniqKey="Attwood A" first="Antony" last="Attwood">Antony Attwood</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Bariana, Tadbir" sort="Bariana, Tadbir" uniqKey="Bariana T" first="Tadbir" last="Bariana">Tadbir Bariana</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Haematology, University College London Cancer Institute, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University College London Cancer Institute, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London</wicri:regionArea></affiliation></author><author><name sortKey="De Bono, Bernard" sort="De Bono, Bernard" uniqKey="De Bono B" first="Bernard" last="De Bono">Bernard De Bono</name><affiliation wicri:level="1"><nlm:aff id="A10">CHIME Institute, University College London, Archway Campus, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>CHIME Institute, University College London, Archway Campus, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Auckland Bioengineering Institute, University of Auckland, New Zealand</nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Auckland Bioengineering Institute, University of Auckland</wicri:regionArea></affiliation></author><author><name sortKey="Breschi, Alessandra" sort="Breschi, Alessandra" uniqKey="Breschi A" first="Alessandra" last="Breschi">Alessandra Breschi</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C." last="Chambers">John C. Chambers</name><affiliation wicri:level="1"><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial College Healthcare NHS Trust, DuCane Road, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ealing Hospital NHS Trust, Southall, Middlesex</wicri:regionArea></affiliation></author><author><name sortKey="Consortium, Bridge" sort="Consortium, Bridge" uniqKey="Consortium B" first="Bridge" last="Consortium">Bridge Consortium</name></author><author><name sortKey="Choudry, Fizzah A" sort="Choudry, Fizzah A" uniqKey="Choudry F" first="Fizzah A." last="Choudry">Fizzah A. Choudry</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Laura" sort="Clarke, Laura" uniqKey="Clarke L" first="Laura" last="Clarke">Laura Clarke</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Coupland, Paul" sort="Coupland, Paul" uniqKey="Coupland P" first="Paul" last="Coupland">Paul Coupland</name><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Ent, Martijn" sort="Van Der Ent, Martijn" uniqKey="Van Der Ent M" first="Martijn" last="Van Der Ent">Martijn Van Der Ent</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Erber, Wendy N" sort="Erber, Wendy N" uniqKey="Erber W" first="Wendy N." last="Erber">Wendy N. Erber</name><affiliation wicri:level="1"><nlm:aff id="A15">Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia</wicri:regionArea></affiliation></author><author><name sortKey="Jansen, Joop H" sort="Jansen, Joop H" uniqKey="Jansen J" first="Joop H." last="Jansen">Joop H. Jansen</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Favier, Remi" sort="Favier, Remi" uniqKey="Favier R" first="Rémi" last="Favier">Rémi Favier</name><affiliation wicri:level="1"><nlm:aff id="A17">Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif</wicri:regionArea></affiliation></author><author><name sortKey="Fenech, Matthew E" sort="Fenech, Matthew E" uniqKey="Fenech M" first="Matthew E." last="Fenech">Matthew E. Fenech</name><affiliation wicri:level="1"><nlm:aff id="A18">Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich</wicri:regionArea></affiliation></author><author><name sortKey="Foad, Nicola" sort="Foad, Nicola" uniqKey="Foad N" first="Nicola" last="Foad">Nicola Foad</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Freson, Kathleen" sort="Freson, Kathleen" uniqKey="Freson K" first="Kathleen" last="Freson">Kathleen Freson</name><affiliation wicri:level="1"><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Molecular and Vascular Biology, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Van Geet, Chris" sort="Van Geet, Chris" uniqKey="Van Geet C" first="Chris" last="Van Geet">Chris Van Geet</name><affiliation wicri:level="1"><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Molecular and Vascular Biology, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Gomez, Keith" sort="Gomez, Keith" uniqKey="Gomez K" first="Keith" last="Gomez">Keith Gomez</name><affiliation wicri:level="1"><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London</wicri:regionArea></affiliation></author><author><name sortKey="Guigo, Roderic" sort="Guigo, Roderic" uniqKey="Guigo R" first="Roderic" last="Guigo">Roderic Guigo</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Hampshire, Daniel" sort="Hampshire, Daniel" uniqKey="Hampshire D" first="Daniel" last="Hampshire">Daniel Hampshire</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kelly, Anne M" sort="Kelly, Anne M" uniqKey="Kelly A" first="Anne M." last="Kelly">Anne M. Kelly</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A20">Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Kerstens, Hindrik H D" sort="Kerstens, Hindrik H D" uniqKey="Kerstens H" first="Hindrik H. D." last="Kerstens">Hindrik H. D. Kerstens</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S." last="Kooner">Jaspal S. Kooner</name><affiliation wicri:level="1"><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial College Healthcare NHS Trust, DuCane Road, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ealing Hospital NHS Trust, Southall, Middlesex</wicri:regionArea></affiliation></author><author><name sortKey="Laffan, Michael" sort="Laffan, Michael" uniqKey="Laffan M" first="Michael" last="Laffan">Michael Laffan</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Lentaigne, Claire" sort="Lentaigne, Claire" uniqKey="Lentaigne C" first="Claire" last="Lentaigne">Claire Lentaigne</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Labalette, Charlotte" sort="Labalette, Charlotte" uniqKey="Labalette C" first="Charlotte" last="Labalette">Charlotte Labalette</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Martin, Tiphaine" sort="Martin, Tiphaine" uniqKey="Martin T" first="Tiphaine" last="Martin">Tiphaine Martin</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A22">Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London</wicri:regionArea></affiliation></author><author><name sortKey="Meacham, Stuart" sort="Meacham, Stuart" uniqKey="Meacham S" first="Stuart" last="Meacham">Stuart Meacham</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Mumford, Andrew" sort="Mumford, Andrew" uniqKey="Mumford A" first="Andrew" last="Mumford">Andrew Mumford</name><affiliation wicri:level="1"><nlm:aff id="A23">School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Cellular and Molecular Medicine, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Nurnberg, Sylvia" sort="Nurnberg, Sylvia" uniqKey="Nurnberg S" first="Sylvia" last="Nürnberg">Sylvia Nürnberg</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Palumbo, Emilio" sort="Palumbo, Emilio" uniqKey="Palumbo E" first="Emilio" last="Palumbo">Emilio Palumbo</name><affiliation wicri:level="1"><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Reijden, Bert A" sort="Van Der Reijden, Bert A" uniqKey="Van Der Reijden B" first="Bert A." last="Van Der Reijden">Bert A. Van Der Reijden</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Richardson, David" sort="Richardson, David" uniqKey="Richardson D" first="David" last="Richardson">David Richardson</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Sammut, Stephen J" sort="Sammut, Stephen J" uniqKey="Sammut S" first="Stephen J." last="Sammut">Stephen J. Sammut</name><affiliation wicri:level="1"><nlm:aff id="A24">Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A25">Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Slodkowicz, Greg" sort="Slodkowicz, Greg" uniqKey="Slodkowicz G" first="Greg" last="Slodkowicz">Greg Slodkowicz</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Tamuri, Asif U" sort="Tamuri, Asif U" uniqKey="Tamuri A" first="Asif U." last="Tamuri">Asif U. Tamuri</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Vasquez, Louella" sort="Vasquez, Louella" uniqKey="Vasquez L" first="Louella" last="Vasquez">Louella Vasquez</name><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Voss, Katrin" sort="Voss, Katrin" uniqKey="Voss K" first="Katrin" last="Voss">Katrin Voss</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Watt, Stephen" sort="Watt, Stephen" uniqKey="Watt S" first="Stephen" last="Watt">Stephen Watt</name><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Westbury, Sarah" sort="Westbury, Sarah" uniqKey="Westbury S" first="Sarah" last="Westbury">Sarah Westbury</name><affiliation wicri:level="1"><nlm:aff id="A26">School of Clinical Sciences, University of Bristol, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Clinical Sciences, University of Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Loos, Remco" sort="Loos, Remco" uniqKey="Loos R" first="Remco" last="Loos">Remco Loos</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Goldman, Nick" sort="Goldman, Nick" uniqKey="Goldman N" first="Nick" last="Goldman">Nick Goldman</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Bertone, Paul" sort="Bertone, Paul" uniqKey="Bertone P" first="Paul" last="Bertone">Paul Bertone</name><affiliation wicri:level="1"><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A27">Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A28">Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Read, Randy J" sort="Read, Randy J" uniqKey="Read R" first="Randy J." last="Read">Randy J. Read</name><affiliation wicri:level="1"><nlm:aff id="A29">Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Richardson, Sylvia" sort="Richardson, Sylvia" uniqKey="Richardson S" first="Sylvia" last="Richardson">Sylvia Richardson</name><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Cvejic, Ana" sort="Cvejic, Ana" uniqKey="Cvejic A" first="Ana" last="Cvejic">Ana Cvejic</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Stunnenberg, Hendrik G" sort="Stunnenberg, Hendrik G" uniqKey="Stunnenberg H" first="Hendrik G." last="Stunnenberg">Hendrik G. Stunnenberg</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Molecular Biology, Radboud University, Nijmegen</wicri:regionArea></affiliation></author><author><name sortKey="Frontini, Mattia" sort="Frontini, Mattia" uniqKey="Frontini M" first="Mattia" last="Frontini">Mattia Frontini</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Rendon, Augusto" sort="Rendon, Augusto" uniqKey="Rendon A" first="Augusto" last="Rendon">Augusto Rendon</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge</wicri:regionArea></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="ISSN">0036-8075</idno><idno type="eISSN">1095-9203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P5">Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identify extensive cell-type specific expression changes: 6,711 genes and 10,724 transcripts, enriched in non-protein coding elements at early stages of differentiation. In addition, we discovered 7,881 novel splice junctions and 2,301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrate experimentally cell specific isoform usage, identifying NFIB as a regulator of megakaryocyte maturation – the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0404511</journal-id><journal-id journal-id-type="pubmed-jr-id">7473</journal-id><journal-id journal-id-type="nlm-ta">Science</journal-id><journal-id journal-id-type="iso-abbrev">Science</journal-id><journal-title-group><journal-title>Science (New York, N.Y.)</journal-title></journal-title-group><issn pub-type="ppub">0036-8075</issn><issn pub-type="epub">1095-9203</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25258084</article-id><article-id pub-id-type="pmc">4254742</article-id><article-id pub-id-type="doi">10.1126/science.1251033</article-id><article-id pub-id-type="manuscript">EMS60870</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Transcriptional diversity during lineage commitment of human blood progenitors</article-title></title-group><contrib-group><contrib contrib-type="author" 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contrib-type="author"><name><surname>Westbury</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Flicek</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Loos</surname><given-names>Remco</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Goldman</surname><given-names>Nick</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Bertone</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A27">27</xref><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Read</surname><given-names>Randy J.</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Richardson</surname><given-names>Sylvia</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Cvejic</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Soranzo</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Ouwehand</surname><given-names>Willem H.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Stunnenberg</surname><given-names>Hendrik G.</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Frontini</surname><given-names>Mattia</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Rendon</surname><given-names>Augusto</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</aff><aff id="A2"><label>2</label>Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A3"><label>3</label>NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A4"><label>4</label>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</aff><aff id="A5"><label>5</label>Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</aff><aff id="A6"><label>6</label>Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A7"><label>7</label>Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom</aff><aff id="A8"><label>8</label>Department of Haematology, University College London Cancer Institute, London, United Kingdom</aff><aff id="A9"><label>9</label>The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</aff><aff id="A10"><label>10</label>CHIME Institute, University College London, Archway Campus, London, United Kingdom</aff><aff id="A11"><label>11</label>Auckland Bioengineering Institute, University of Auckland, New Zealand</aff><aff id="A12"><label>12</label>Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</aff><aff id="A13"><label>13</label>Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</aff><aff id="A14"><label>14</label>Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</aff><aff id="A15"><label>15</label>Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia</aff><aff id="A16"><label>16</label>Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</aff><aff id="A17"><label>17</label>Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France</aff><aff id="A18"><label>18</label>Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom</aff><aff id="A19"><label>19</label>Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</aff><aff id="A20"><label>20</label>Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A21"><label>21</label>Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</aff><aff id="A22"><label>22</label>Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London, United Kingdom</aff><aff id="A23"><label>23</label>School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom</aff><aff id="A24"><label>24</label>Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A25"><label>25</label>Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><aff id="A26"><label>26</label>School of Clinical Sciences, University of Bristol, United Kingdom</aff><aff id="A27"><label>27</label>Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany</aff><aff id="A28"><label>28</label>Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom</aff><aff id="A29"><label>29</label>Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</aff><author-notes><corresp id="CR1"><label>*</label>Correspondence to: <email>ar506@cam.ac.uk</email> (A.R.), <email>mf471@cam.ac.uk</email> (M.F.)</corresp><fn id="FN1"><label>‡</label><p id="P1">A list of the members of the BRIDGE Bleeding and Platelet Disorders Consortium is available from <xref ref-type="supplementary-material" rid="SD2">Supplementary Materials</xref>.</p></fn><fn fn-type="present-address" id="FN2"><label>§</label><p id="P2">Sylvia Nürnberg is currently at Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.</p></fn><fn fn-type="present-address" id="FN3"><label>¶</label><p id="P3">Katrin Voss is currently at Loxxess Neuburg GmbH, Augsburger Straße 133, 86633 Neuburg an der Donau, Germany.</p></fn><fn fn-type="present-address" id="FN4"><label>±</label><p id="P4">Tiphaine Martin is currently at the Department of Twin Research & Genetic Epidemiology, Genetics & Molecular Medicine Division, St Thomas’ Hospital, King’s College, London, United Kingdom.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>11</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>26</day><month>9</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>26</day><month>3</month><year>2015</year></pub-date><volume>345</volume><issue>6204</issue><fpage>1251033</fpage><lpage>1251033</lpage><pmc-comment>elocation-id from pubmed: 10.1126/science.1251033</pmc-comment>
<abstract><p id="P5">Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identify extensive cell-type specific expression changes: 6,711 genes and 10,724 transcripts, enriched in non-protein coding elements at early stages of differentiation. In addition, we discovered 7,881 novel splice junctions and 2,301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrate experimentally cell specific isoform usage, identifying NFIB as a regulator of megakaryocyte maturation – the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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