Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells
Identifieur interne : 000014 ( Main/Exploration ); précédent : 000013; suivant : 000015Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells
Auteurs : Iain C. Macaulay [Royaume-Uni] ; Valentine Svensson [Royaume-Uni] ; Charlotte Labalette [Royaume-Uni] ; Lauren Ferreira [Royaume-Uni] ; Fiona Hamey [Royaume-Uni] ; Thierry Voet [Royaume-Uni, Belgique] ; Sarah A. Teichmann [Royaume-Uni] ; Ana Cvejic [Royaume-Uni]Source :
- Cell Reports [ 2211-1247 ] ; 2016.
Abstract
The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment.
Url:
DOI: 10.1016/j.celrep.2015.12.082
PubMed: 26804912
PubMed Central: 4742565
Affiliations:
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Institute, Cambridge CB2 1QR, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR</wicri:regionArea><wicri:noRegion>Cambridge CB2 1QR</wicri:noRegion></affiliation></author><author><name sortKey="Voet, Thierry" sort="Voet, Thierry" uniqKey="Voet T" first="Thierry" last="Voet">Thierry Voet</name><affiliation wicri:level="1"><nlm:aff id="aff1">Sanger Institute–EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Sanger Institute–EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH</wicri:regionArea><wicri:noRegion>Cambridge CB10 1HH</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Human Genetics, University of Leuven, Leuven 3000, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Human Genetics, University of Leuven, Leuven 3000</wicri:regionArea><wicri:noRegion>Leuven 3000</wicri:noRegion></affiliation></author><author><name sortKey="Teichmann, Sarah A" sort="Teichmann, Sarah A" uniqKey="Teichmann S" first="Sarah A." last="Teichmann">Sarah A. Teichmann</name><affiliation wicri:level="1"><nlm:aff id="aff2">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH</wicri:regionArea><wicri:noRegion>Cambridge CB10 1HH</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD</wicri:regionArea><wicri:noRegion>Cambridge CB10 1SD</wicri:noRegion></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="aff2">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH</wicri:regionArea><wicri:noRegion>Cambridge CB10 1HH</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge CB2 0PT</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR</wicri:regionArea><wicri:noRegion>Cambridge CB2 1QR</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell Reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bielczyk Maczy Ska, E" uniqKey="Bielczyk Maczy Ska E">E. Bielczyk-Maczyńska</name></author><author><name sortKey="Serbanovic Canic, J" uniqKey="Serbanovic Canic J">J. Serbanovic-Canic</name></author><author><name sortKey="Ferreira, L" uniqKey="Ferreira L">L. Ferreira</name></author><author><name sortKey="Soranzo, N" uniqKey="Soranzo N">N. Soranzo</name></author><author><name sortKey="Stemple, D L" uniqKey="Stemple D">D.L. Stemple</name></author><author><name sortKey="Ouwehand, W H" uniqKey="Ouwehand W">W.H. Ouwehand</name></author><author><name sortKey="Cvejic, A" uniqKey="Cvejic A">A. Cvejic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Capron, C" uniqKey="Capron C">C. 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Teichmann</name><name sortKey="Teichmann, Sarah A" sort="Teichmann, Sarah A" uniqKey="Teichmann S" first="Sarah A." last="Teichmann">Sarah A. Teichmann</name><name sortKey="Voet, Thierry" sort="Voet, Thierry" uniqKey="Voet T" first="Thierry" last="Voet">Thierry Voet</name></country><country name="Belgique"><noRegion><name sortKey="Voet, Thierry" sort="Voet, Thierry" uniqKey="Voet T" first="Thierry" last="Voet">Thierry Voet</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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