| Literature DB >> 25258084 |
Lu Chen1,2,3, Myrto Kostadima2,4,3, Joost H A Martens5, Nicole Soranzo1,2, Willem H Ouwehand2,3,1, Hendrik G Stunnenberg5, Mattia Frontini2,3, Augusto Rendon2,3,6, Giovanni Canu2,3, Sara P Garcia2,3, Ernest Turro2,3, Kate Downes2,3, Iain C Macaulay7, Ewa Bielczyk-Maczynska2,3, Sophia Coe2,3, Samantha Farrow2,3, Pawan Poudel2,3, Frances Burden2,3, Sjoert B G Jansen2,3, William J Astle2,3,6, Antony Attwood2,3, Tadbir Bariana8,9, Bernard de Bono10,11, Alessandra Breschi12, John C Chambers13,14, Bridge Consortium1, Fizzah A Choudry2,3, Laura Clarke4, Paul Coupland1, Martijn van der Ent5, Wendy N Erber15, Joop H Jansen16, Rémi Favier17, Matthew E Fenech18, Nicola Foad2,3, Kathleen Freson19, Chris van Geet19, Keith Gomez9, Roderic Guigo12, Daniel Hampshire2,3, Anne M Kelly2,3,20, Hindrik H D Kerstens5, Jaspal S Kooner13,14, Michael Laffan21, Claire Lentaigne21, Charlotte Labalette2,3, Tiphaine Martin2,3,22, Stuart Meacham2,3, Andrew Mumford23, Sylvia Nürnberg2,3, Emilio Palumbo12, Bert A van der Reijden16, David Richardson4, Stephen J Sammut24,25, Greg Slodkowicz4, Asif U Tamuri4, Louella Vasquez3, Katrin Voss2,3, Stephen Watt3, Sarah Westbury26, Paul Flicek4,1, Remco Loos4, Nick Goldman4, Paul Bertone4,27,28, Randy J Read29, Sylvia Richardson6, Ana Cvejic2,1.
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 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.Entities:
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Year: 2014 PMID： 25258084 PMCID： PMC4254742 DOI： 10.1126/science.1251033
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728