Transcriptional diversity during lineage commitment of human blood progenitors

Lu Clien, Myrto Kostadraia, Joost H.A. Martens, Giovanni Canu, Sara P. Garcia, Ernest Torro, Kate Downes, Lain C. Macaolay, Ewa Bielczyk-Maezynska, Sophia Coe, Samantha Farrow, Pawan Poudel, Frances Borden, Sjoert B.G. Jansen, William J. Astle, Antony Attwood, Tadbir Bariana, Bernard De Bono, Alessandra Bresechi, John C. ChambersFizzah A. Choudry, Laura Clarke, Paud 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, Roderiec Guigo, Daniel Hampshire, Anne M. Kelly, Hindrik H.D. Kerstens, Jaspal S. Kooner, Michael Laffan, Claire Lentaigne, Charlotte Labalette, Tiphaine Martin, Stuart Meaeham, Andrew Mumford, Sylvia Nuiirnberg, Emilio Palumbo, Bert A. Van Der Reijden, David Richardson, Stephen J. Sammut, Greg Slodkowicz, Asif U. Tamuri, Loueulla Vasquez, Katrin Voss, Stephen Watt, Sarah Westbury, Paul Flicek, Remeo Loos, Nick Goldman, Paul Bertone, Randy J. Read, Sylvia Richardson, Ana Cvejic, Nicole Soranzo, Willem H. Onwehand, Hendrik G. Stunnenberg, Mattia Frontini, Augusto Rendon

Research output: Contribution to journalArticlepeer-review

209 Citations (Scopus)

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 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 l/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.

Original languageEnglish
Article number1251033
JournalScience
Volume345
Issue number6204
DOIs
Publication statusPublished - 26 Sept 2014
Externally publishedYes

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