Transcriptional diversity during lineage commitment of human blood progenitors
Identifieur interne : 001D21 ( Pmc/Corpus ); précédent : 001D20; suivant : 001D22Transcriptional diversity during lineage commitment of human blood progenitors
Auteurs : Lu Chen ; Myrto Kostadima ; Joost H. A. Martens ; Giovanni Canu ; Sara P. Garcia ; Ernest Turro ; Kate Downes ; Iain C. Macaulay ; Ewa Bielczyk-Maczynska ; Sophia Coe ; Samantha Farrow ; Pawan Poudel ; Frances Burden ; Sjoert B. G. Jansen ; William J. Astle ; Antony Attwood ; Tadbir Bariana ; Bernard De Bono ; Alessandra Breschi ; John C. Chambers ; Bridge Consortium ; Fizzah A. Choudry ; Laura Clarke ; Paul Coupland ; Martijn Van Der Ent ; Wendy N. Erber ; Joop H. Jansen ; Rémi Favier ; Matthew E. Fenech ; Nicola Foad ; Kathleen Freson ; Chris Van Geet ; Keith Gomez ; Roderic Guigo ; Daniel Hampshire ; Anne M. Kelly ; Hindrik H. D. Kerstens ; Jaspal S. Kooner ; Michael Laffan ; Claire Lentaigne ; Charlotte Labalette ; Tiphaine Martin ; Stuart Meacham ; Andrew Mumford ; Sylvia Nürnberg ; Emilio Palumbo ; Bert A. Van Der Reijden ; David Richardson ; Stephen J. Sammut ; Greg Slodkowicz ; Asif U. Tamuri ; Louella Vasquez ; Katrin Voss ; Stephen Watt ; Sarah Westbury ; Paul Flicek ; Remco Loos ; Nick Goldman ; Paul Bertone ; Randy J. Read ; Sylvia Richardson ; Ana Cvejic ; Nicole Soranzo ; Willem H. Ouwehand ; Hendrik G. Stunnenberg ; Mattia Frontini ; Augusto RendonSource :
- 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
Links to Exploration step
PMC:4254742Le document en format XML
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<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
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<author><name sortKey="Kostadima, Myrto" sort="Kostadima, Myrto" uniqKey="Kostadima M" first="Myrto" last="Kostadima">Myrto Kostadima</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Canu, Giovanni" sort="Canu, Giovanni" uniqKey="Canu G" first="Giovanni" last="Canu">Giovanni Canu</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
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<author><name sortKey="Garcia, Sara P" sort="Garcia, Sara P" uniqKey="Garcia S" first="Sara P." last="Garcia">Sara P. Garcia</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Turro, Ernest" sort="Turro, Ernest" uniqKey="Turro E" first="Ernest" last="Turro">Ernest Turro</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Downes, Kate" sort="Downes, Kate" uniqKey="Downes K" first="Kate" last="Downes">Kate Downes</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Macaulay, Iain C" sort="Macaulay, Iain C" uniqKey="Macaulay I" first="Iain C." last="Macaulay">Iain C. Macaulay</name>
<affiliation><nlm:aff id="A7">Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Bielczyk Maczynska, Ewa" sort="Bielczyk Maczynska, Ewa" uniqKey="Bielczyk Maczynska E" first="Ewa" last="Bielczyk-Maczynska">Ewa Bielczyk-Maczynska</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Coe, Sophia" sort="Coe, Sophia" uniqKey="Coe S" first="Sophia" last="Coe">Sophia Coe</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Farrow, Samantha" sort="Farrow, Samantha" uniqKey="Farrow S" first="Samantha" last="Farrow">Samantha Farrow</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
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<author><name sortKey="Poudel, Pawan" sort="Poudel, Pawan" uniqKey="Poudel P" first="Pawan" last="Poudel">Pawan Poudel</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Burden, Frances" sort="Burden, Frances" uniqKey="Burden F" first="Frances" last="Burden">Frances Burden</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Attwood, Antony" sort="Attwood, Antony" uniqKey="Attwood A" first="Antony" last="Attwood">Antony Attwood</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bariana, Tadbir" sort="Bariana, Tadbir" uniqKey="Bariana T" first="Tadbir" last="Bariana">Tadbir Bariana</name>
<affiliation><nlm:aff id="A8">Department of Haematology, University College London Cancer Institute, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff>
</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><nlm:aff id="A10">CHIME Institute, University College London, Archway Campus, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A11">Auckland Bioengineering Institute, University of Auckland, New Zealand</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Breschi, Alessandra" sort="Breschi, Alessandra" uniqKey="Breschi A" first="Alessandra" last="Breschi">Alessandra Breschi</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</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><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Clarke, Laura" sort="Clarke, Laura" uniqKey="Clarke L" first="Laura" last="Clarke">Laura Clarke</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coupland, Paul" sort="Coupland, Paul" uniqKey="Coupland P" first="Paul" last="Coupland">Paul Coupland</name>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</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><nlm:aff id="A15">Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia</nlm:aff>
</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><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Favier, Remi" sort="Favier, Remi" uniqKey="Favier R" first="Rémi" last="Favier">Rémi Favier</name>
<affiliation><nlm:aff id="A17">Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France</nlm:aff>
</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><nlm:aff id="A18">Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Foad, Nicola" sort="Foad, Nicola" uniqKey="Foad N" first="Nicola" last="Foad">Nicola Foad</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Freson, Kathleen" sort="Freson, Kathleen" uniqKey="Freson K" first="Kathleen" last="Freson">Kathleen Freson</name>
<affiliation><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff>
</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><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gomez, Keith" sort="Gomez, Keith" uniqKey="Gomez K" first="Keith" last="Gomez">Keith Gomez</name>
<affiliation><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guigo, Roderic" sort="Guigo, Roderic" uniqKey="Guigo R" first="Roderic" last="Guigo">Roderic Guigo</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hampshire, Daniel" sort="Hampshire, Daniel" uniqKey="Hampshire D" first="Daniel" last="Hampshire">Daniel Hampshire</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A20">Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</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><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laffan, Michael" sort="Laffan, Michael" uniqKey="Laffan M" first="Michael" last="Laffan">Michael Laffan</name>
<affiliation><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lentaigne, Claire" sort="Lentaigne, Claire" uniqKey="Lentaigne C" first="Claire" last="Lentaigne">Claire Lentaigne</name>
<affiliation><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Labalette, Charlotte" sort="Labalette, Charlotte" uniqKey="Labalette C" first="Charlotte" last="Labalette">Charlotte Labalette</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Martin, Tiphaine" sort="Martin, Tiphaine" uniqKey="Martin T" first="Tiphaine" last="Martin">Tiphaine Martin</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Meacham, Stuart" sort="Meacham, Stuart" uniqKey="Meacham S" first="Stuart" last="Meacham">Stuart Meacham</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mumford, Andrew" sort="Mumford, Andrew" uniqKey="Mumford A" first="Andrew" last="Mumford">Andrew Mumford</name>
<affiliation><nlm:aff id="A23">School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nurnberg, Sylvia" sort="Nurnberg, Sylvia" uniqKey="Nurnberg S" first="Sylvia" last="Nürnberg">Sylvia Nürnberg</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Palumbo, Emilio" sort="Palumbo, Emilio" uniqKey="Palumbo E" first="Emilio" last="Palumbo">Emilio Palumbo</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</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><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richardson, David" sort="Richardson, David" uniqKey="Richardson D" first="David" last="Richardson">David Richardson</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A24">Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A25">Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slodkowicz, Greg" sort="Slodkowicz, Greg" uniqKey="Slodkowicz G" first="Greg" last="Slodkowicz">Greg Slodkowicz</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vasquez, Louella" sort="Vasquez, Louella" uniqKey="Vasquez L" first="Louella" last="Vasquez">Louella Vasquez</name>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voss, Katrin" sort="Voss, Katrin" uniqKey="Voss K" first="Katrin" last="Voss">Katrin Voss</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Watt, Stephen" sort="Watt, Stephen" uniqKey="Watt S" first="Stephen" last="Watt">Stephen Watt</name>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Westbury, Sarah" sort="Westbury, Sarah" uniqKey="Westbury S" first="Sarah" last="Westbury">Sarah Westbury</name>
<affiliation><nlm:aff id="A26">School of Clinical Sciences, University of Bristol, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loos, Remco" sort="Loos, Remco" uniqKey="Loos R" first="Remco" last="Loos">Remco Loos</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Goldman, Nick" sort="Goldman, Nick" uniqKey="Goldman N" first="Nick" last="Goldman">Nick Goldman</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bertone, Paul" sort="Bertone, Paul" uniqKey="Bertone P" first="Paul" last="Bertone">Paul Bertone</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A27">Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A29">Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richardson, Sylvia" sort="Richardson, Sylvia" uniqKey="Richardson S" first="Sylvia" last="Richardson">Sylvia Richardson</name>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cvejic, Ana" sort="Cvejic, Ana" uniqKey="Cvejic A" first="Ana" last="Cvejic">Ana Cvejic</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Frontini, Mattia" sort="Frontini, Mattia" uniqKey="Frontini M" first="Mattia" last="Frontini">Mattia Frontini</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rendon, Augusto" sort="Rendon, Augusto" uniqKey="Rendon A" first="Augusto" last="Rendon">Augusto Rendon</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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>
</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><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kostadima, Myrto" sort="Kostadima, Myrto" uniqKey="Kostadima M" first="Myrto" last="Kostadima">Myrto Kostadima</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Canu, Giovanni" sort="Canu, Giovanni" uniqKey="Canu G" first="Giovanni" last="Canu">Giovanni Canu</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Turro, Ernest" sort="Turro, Ernest" uniqKey="Turro E" first="Ernest" last="Turro">Ernest Turro</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Downes, Kate" sort="Downes, Kate" uniqKey="Downes K" first="Kate" last="Downes">Kate Downes</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A7">Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coe, Sophia" sort="Coe, Sophia" uniqKey="Coe S" first="Sophia" last="Coe">Sophia Coe</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Farrow, Samantha" sort="Farrow, Samantha" uniqKey="Farrow S" first="Samantha" last="Farrow">Samantha Farrow</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Poudel, Pawan" sort="Poudel, Pawan" uniqKey="Poudel P" first="Pawan" last="Poudel">Pawan Poudel</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Burden, Frances" sort="Burden, Frances" uniqKey="Burden F" first="Frances" last="Burden">Frances Burden</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Attwood, Antony" sort="Attwood, Antony" uniqKey="Attwood A" first="Antony" last="Attwood">Antony Attwood</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bariana, Tadbir" sort="Bariana, Tadbir" uniqKey="Bariana T" first="Tadbir" last="Bariana">Tadbir Bariana</name>
<affiliation><nlm:aff id="A8">Department of Haematology, University College London Cancer Institute, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff>
</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><nlm:aff id="A10">CHIME Institute, University College London, Archway Campus, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A11">Auckland Bioengineering Institute, University of Auckland, New Zealand</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Breschi, Alessandra" sort="Breschi, Alessandra" uniqKey="Breschi A" first="Alessandra" last="Breschi">Alessandra Breschi</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</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><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Clarke, Laura" sort="Clarke, Laura" uniqKey="Clarke L" first="Laura" last="Clarke">Laura Clarke</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coupland, Paul" sort="Coupland, Paul" uniqKey="Coupland P" first="Paul" last="Coupland">Paul Coupland</name>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</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><nlm:aff id="A15">Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia</nlm:aff>
</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><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Favier, Remi" sort="Favier, Remi" uniqKey="Favier R" first="Rémi" last="Favier">Rémi Favier</name>
<affiliation><nlm:aff id="A17">Assistance Publique-Hopitaux de Paris, Institut National de la Santé et de la Recherche Médicale U1009, Villejuif, France</nlm:aff>
</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><nlm:aff id="A18">Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Foad, Nicola" sort="Foad, Nicola" uniqKey="Foad N" first="Nicola" last="Foad">Nicola Foad</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Freson, Kathleen" sort="Freson, Kathleen" uniqKey="Freson K" first="Kathleen" last="Freson">Kathleen Freson</name>
<affiliation><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff>
</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><nlm:aff id="A19">Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gomez, Keith" sort="Gomez, Keith" uniqKey="Gomez K" first="Keith" last="Gomez">Keith Gomez</name>
<affiliation><nlm:aff id="A9">The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Trust, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guigo, Roderic" sort="Guigo, Roderic" uniqKey="Guigo R" first="Roderic" last="Guigo">Roderic Guigo</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hampshire, Daniel" sort="Hampshire, Daniel" uniqKey="Hampshire D" first="Daniel" last="Hampshire">Daniel Hampshire</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A20">Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</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><nlm:aff id="A13">Imperial College Healthcare NHS Trust, DuCane Road, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A14">Ealing Hospital NHS Trust, Southall, Middlesex, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laffan, Michael" sort="Laffan, Michael" uniqKey="Laffan M" first="Michael" last="Laffan">Michael Laffan</name>
<affiliation><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lentaigne, Claire" sort="Lentaigne, Claire" uniqKey="Lentaigne C" first="Claire" last="Lentaigne">Claire Lentaigne</name>
<affiliation><nlm:aff id="A21">Department of Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Labalette, Charlotte" sort="Labalette, Charlotte" uniqKey="Labalette C" first="Charlotte" last="Labalette">Charlotte Labalette</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Martin, Tiphaine" sort="Martin, Tiphaine" uniqKey="Martin T" first="Tiphaine" last="Martin">Tiphaine Martin</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Meacham, Stuart" sort="Meacham, Stuart" uniqKey="Meacham S" first="Stuart" last="Meacham">Stuart Meacham</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mumford, Andrew" sort="Mumford, Andrew" uniqKey="Mumford A" first="Andrew" last="Mumford">Andrew Mumford</name>
<affiliation><nlm:aff id="A23">School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nurnberg, Sylvia" sort="Nurnberg, Sylvia" uniqKey="Nurnberg S" first="Sylvia" last="Nürnberg">Sylvia Nürnberg</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Palumbo, Emilio" sort="Palumbo, Emilio" uniqKey="Palumbo E" first="Emilio" last="Palumbo">Emilio Palumbo</name>
<affiliation><nlm:aff id="A12">Centre for Genomic Regulation and University Pompeu Fabra, Barcelona, Spain</nlm:aff>
</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><nlm:aff id="A16">Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richardson, David" sort="Richardson, David" uniqKey="Richardson D" first="David" last="Richardson">David Richardson</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A24">Department of Oncology, Addenbrooke’s Cambridge University Hospital NHS Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A25">Cancer Research United Kingdom, Cambridge Institute, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slodkowicz, Greg" sort="Slodkowicz, Greg" uniqKey="Slodkowicz G" first="Greg" last="Slodkowicz">Greg Slodkowicz</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vasquez, Louella" sort="Vasquez, Louella" uniqKey="Vasquez L" first="Louella" last="Vasquez">Louella Vasquez</name>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voss, Katrin" sort="Voss, Katrin" uniqKey="Voss K" first="Katrin" last="Voss">Katrin Voss</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Watt, Stephen" sort="Watt, Stephen" uniqKey="Watt S" first="Stephen" last="Watt">Stephen Watt</name>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Westbury, Sarah" sort="Westbury, Sarah" uniqKey="Westbury S" first="Sarah" last="Westbury">Sarah Westbury</name>
<affiliation><nlm:aff id="A26">School of Clinical Sciences, University of Bristol, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loos, Remco" sort="Loos, Remco" uniqKey="Loos R" first="Remco" last="Loos">Remco Loos</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Goldman, Nick" sort="Goldman, Nick" uniqKey="Goldman N" first="Nick" last="Goldman">Nick Goldman</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bertone, Paul" sort="Bertone, Paul" uniqKey="Bertone P" first="Paul" last="Bertone">Paul Bertone</name>
<affiliation><nlm:aff id="A4">European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A27">Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Heidelberg, Germany</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A28">Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A29">Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Richardson, Sylvia" sort="Richardson, Sylvia" uniqKey="Richardson S" first="Sylvia" last="Richardson">Sylvia Richardson</name>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cvejic, Ana" sort="Cvejic, Ana" uniqKey="Cvejic A" first="Ana" last="Cvejic">Ana Cvejic</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A1">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom</nlm:aff>
</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><nlm:aff id="A5">Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Frontini, Mattia" sort="Frontini, Mattia" uniqKey="Frontini M" first="Mattia" last="Frontini">Mattia Frontini</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rendon, Augusto" sort="Rendon, Augusto" uniqKey="Rendon A" first="Augusto" last="Rendon">Augusto Rendon</name>
<affiliation><nlm:aff id="A2">Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A6">Medical Research Council Biostatistics Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom</nlm:aff>
</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" equal-contrib="yes"><name><surname>Chen</surname>
<given-names>Lu</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Kostadima</surname>
<given-names>Myrto</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Martens</surname>
<given-names>Joost H.A.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Canu</surname>
<given-names>Giovanni</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Garcia</surname>
<given-names>Sara P.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Turro</surname>
<given-names>Ernest</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Downes</surname>
<given-names>Kate</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Macaulay</surname>
<given-names>Iain C.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bielczyk-Maczynska</surname>
<given-names>Ewa</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coe</surname>
<given-names>Sophia</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Farrow</surname>
<given-names>Samantha</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Poudel</surname>
<given-names>Pawan</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Burden</surname>
<given-names>Frances</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jansen</surname>
<given-names>Sjoert B.G.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Astle</surname>
<given-names>William J.</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>
</contrib>
<contrib contrib-type="author"><name><surname>Attwood</surname>
<given-names>Antony</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bariana</surname>
<given-names>Tadbir</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Bono</surname>
<given-names>Bernard</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Breschi</surname>
<given-names>Alessandra</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chambers</surname>
<given-names>John C.</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Consortium</surname>
<given-names>BRIDGE</given-names>
</name>
<xref ref-type="author-notes" rid="FN1">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Choudry</surname>
<given-names>Fizzah A.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clarke</surname>
<given-names>Laura</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coupland</surname>
<given-names>Paul</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van der Ent</surname>
<given-names>Martijn</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Erber</surname>
<given-names>Wendy N.</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jansen</surname>
<given-names>Joop H.</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Favier</surname>
<given-names>Rémi</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fenech</surname>
<given-names>Matthew E.</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Foad</surname>
<given-names>Nicola</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Freson</surname>
<given-names>Kathleen</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Geet</surname>
<given-names>Chris</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gomez</surname>
<given-names>Keith</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Guigo</surname>
<given-names>Roderic</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hampshire</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kelly</surname>
<given-names>Anne M.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kerstens</surname>
<given-names>Hindrik H.D.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kooner</surname>
<given-names>Jaspal S.</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Laffan</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lentaigne</surname>
<given-names>Claire</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Labalette</surname>
<given-names>Charlotte</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martin</surname>
<given-names>Tiphaine</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A22">22</xref>
<xref ref-type="author-notes" rid="FN4">±</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meacham</surname>
<given-names>Stuart</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mumford</surname>
<given-names>Andrew</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nürnberg</surname>
<given-names>Sylvia</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="author-notes" rid="FN2">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palumbo</surname>
<given-names>Emilio</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van der Reijden</surname>
<given-names>Bert A.</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Richardson</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sammut</surname>
<given-names>Stephen J.</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Slodkowicz</surname>
<given-names>Greg</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tamuri</surname>
<given-names>Asif U.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vasquez</surname>
<given-names>Louella</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Voss</surname>
<given-names>Katrin</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="author-notes" rid="FN3">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Watt</surname>
<given-names>Stephen</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib 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>
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