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Authors: Chen, Lu and Kostadima, Myrto and Martens, Joost H A and Canu, Giovanni and Garcia, Sara P and Turro, Ernest and Downes, Kate and Macaulay, Iain C and Bielczyk-Maczynska, Ewa and Coe, Sophia and Farrow, Samantha and Poudel, Pawan and Burden, Frances and Jansen, Sjoert B G and Astle, William J and Attwood, Antony and Bariana, Tadbir and de Bono, Bernard and Breschi, Alessandra and Chambers, John C and Choudry, Fizzah A and Clarke, Laura and Coupland, Paul and van der Ent, Martijn and Erber, Wendy N and Jansen, Joop H and Favier, Rémi and Fenech, Matthew E and Foad, Nicola and Freson, Kathleen and van Geet, Chris and Gomez, Keith and Guigo, Roderic and Hampshire, Daniel and Kelly, Anne M and Kerstens, Hindrik H D and Kooner, Jaspal S and Laffan, Michael and Lentaigne, Claire and Labalette, Charlotte and Martin, Tiphaine and Meacham, Stuart and Mumford, Andrew and Nürnberg, Sylvia and Palumbo, Emilio and van der Reijden, Bert A and Richardson, David and Sammut, Stephen J and Slodkowicz, Greg and Tamuri, Asif U and Vasquez, Louella and Voss, Katrin and Watt, Stephen and Westbury, Sarah and Flicek, Paul and Loos, Remco and Goldman, Nick and Bertone, Paul and Read, Randy J and Richardson, Sylvia and Cvejic, Ana and Soranzo, Nicole and Ouwehand, Willem H and Stunnenberg, Hendrik G and Frontini, Mattia and Rendon, Augusto

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. Copyright © 2014, American Association for the Advancement of Science.

Journal: Science
DOI: 10.1126/science.1251033
Year: 2014

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