Transcriptional diversity during lineage commitment of human blood progenitors

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 stag...

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Detalhes bibliográficos
Autores: Chen, Lu, Breschi, Alessandra, 1988-, Guigó Serra, Roderic, Palumbo, Emilio, Rendon, Augusto
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/41853
Acesso em linha:http://hdl.handle.net/10230/41853
http://dx.doi.org/10.1126/science.1251033
Access Level:acceso abierto
Palavra-chave:Empalmament alternatiu
llinatge cel·lular
Hematopoesi
Cèl·lules mare hematopoètiques
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spelling Transcriptional diversity during lineage commitment of human blood progenitorsChen, LuBreschi, Alessandra, 1988-Guigó Serra, RodericPalumbo, EmilioRendon, AugustoEmpalmament alternatiullinatge cel·lularHematopoesiCèl·lules mare hematopoètiquesBlood 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 identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (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.The work described in this manuscript was primarily supported by the European Commission Seventh Framework Program through the BLUEPRINT grant with code HEALTH-F5-2011-282510 (DH, FB, GC, JHAM, KD, LC, MF, SC, SF and SPG). Research in the Ouwehand laboratory is further supported by program grants from the National Institute for Health Research (NIHR, http://www.nihr.ac.uk; to AA, MK, PP, SBGJ, SN, and WHO); and the British Heart Foundation under numbers RP-PG-0310-1002 and RG/09/12/28096 (http://www.bhf.org.uk; to AR and WJA). KF and MK were supported by Marie Curie funding from the NETSIM FP7 program funded by the European Commission. The Cambridge BioResource (http://www.cambridgebioresource.org.uk), the Cell Phenotyping Hub, and the Cambridge Translational GenOmics laboratory (http://www.catgo.org.uk) are supported by an NIHR grant to the Cambridge NIHR Biomedical Research Centre (BRC). Research in the Soranzo laboratory (LV, NS and SW) is further supported by the Wellcome Trust (Grant Codes WT098051 and WT091310) and the EU FP7 EPIGENESYS initiative (Grant Code 257082). Research in the Cvejic laboratory (AC and CL) is funded by the Cancer Research UK under grant number C45041/A14953. SJS is funded by NIHR. MEF is supported by a British Heart Foundation Clinical Research Training Fellowship, number FS/12/27/29405. EBM is supported by a Wellcome Trust grant, number 084183/Z/07/Z. FAC, CL and SW are supported by MRC Clinical Training Fellowships and TB by a British Society of Haematology/NHS Blood and Transplant grant. RJR is a Principal Research Fellow of the Wellcome Trust, grant No. 082961/Z/07/Z. Research in the Flicek laboratory is also supported by the Wellcome Trust (grant number 095908) and EMBL. Research in the Bertone laboratory is supported by EMBL. KF and CvG are supported by FWO-Vlaanderen through grant G.0B17.13NAmerican Association for the Advancement of Science (AAAS)201920192014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/41853http://dx.doi.org/10.1126/science.1251033reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésScience. 2014 Sep 26;345(6204):1251033info:eu-repo/grantAgreement/EC/FP7/282510info:eu-repo/grantAgreement/EC/FP7/215820info:eu-repo/grantAgreement/EC/FP7/257082This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on vol. 345, num. 6204, 2014. DOI: 10.1126/science.1251033info:eu-repo/semantics/openAccessoai:recercat.cat:10230/418532026-05-29T05:05:01Z
dc.title.none.fl_str_mv Transcriptional diversity during lineage commitment of human blood progenitors
title Transcriptional diversity during lineage commitment of human blood progenitors
spellingShingle Transcriptional diversity during lineage commitment of human blood progenitors
Chen, Lu
Empalmament alternatiu
llinatge cel·lular
Hematopoesi
Cèl·lules mare hematopoètiques
title_short Transcriptional diversity during lineage commitment of human blood progenitors
title_full Transcriptional diversity during lineage commitment of human blood progenitors
title_fullStr Transcriptional diversity during lineage commitment of human blood progenitors
title_full_unstemmed Transcriptional diversity during lineage commitment of human blood progenitors
title_sort Transcriptional diversity during lineage commitment of human blood progenitors
dc.creator.none.fl_str_mv Chen, Lu
Breschi, Alessandra, 1988-
Guigó Serra, Roderic
Palumbo, Emilio
Rendon, Augusto
author Chen, Lu
author_facet Chen, Lu
Breschi, Alessandra, 1988-
Guigó Serra, Roderic
Palumbo, Emilio
Rendon, Augusto
author_role author
author2 Breschi, Alessandra, 1988-
Guigó Serra, Roderic
Palumbo, Emilio
Rendon, Augusto
author2_role author
author
author
author
dc.subject.none.fl_str_mv Empalmament alternatiu
llinatge cel·lular
Hematopoesi
Cèl·lules mare hematopoètiques
topic Empalmament alternatiu
llinatge cel·lular
Hematopoesi
Cèl·lules mare hematopoètiques
description 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 identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (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.
publishDate 2014
dc.date.none.fl_str_mv 2014
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/41853
http://dx.doi.org/10.1126/science.1251033
url http://hdl.handle.net/10230/41853
http://dx.doi.org/10.1126/science.1251033
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Science. 2014 Sep 26;345(6204):1251033
info:eu-repo/grantAgreement/EC/FP7/282510
info:eu-repo/grantAgreement/EC/FP7/215820
info:eu-repo/grantAgreement/EC/FP7/257082
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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