Transcriptional diversity during lineage commitment of human blood progenitors

Chen, Lu, Kostadima, Myrto, Martens, Joost H. A., Canu, Giovanni, Garcia, Sara P., Turro, Ernest, Downes, Kate, Macaulay, Iain C., Bielczyk-Maczynska, Ewa, Coe, Sophia, Farrow, Samantha, Poudel, Pawan, Burden, Frances, Jansen, Sjoert B. G., Astle, William J., Attwood, Antony, Bariana, Tadbir, de Bono, Bernard, Breschi, Alessandra, Chambers, John C., Choudry, Fizzah A., Clarke, Laura, Coupland, Paul, van der Ent, Martjin, Erber, Wendy N., Jansen, Joop H., Favier, Rémi, Fenech, Matthew E., Foad, Nicola, Freson, Kathleen, van Geet, Chris, Gomez, Keith, Guigo, Roderic, Hampshire, Daniel, Kelly, Anne M., Kerstens, Hindrik H. D., Kooner, Jaspal S., Laffan, Michael, Lentaigne, Claire, Labalette, Charlotte, Martin, Tiphaine, Meacham, Stuart, Mumford, Andrew, Nürnberg, Sylvia T., Palumbo, Emilio, van der Reijden, Bert A., Richardson, David, Sammut, Stephen J., Slodkowicz, Greg, Tamuri, Asif U., Vasquez, Louella, Voss, Katrin, Watt, Stephen, Westbury, Sarah, Flicek, Paul, Loos, Remco, Goldman, Nick, Bertone, Paul, Read, Randy J,, Richardson, Sylvia, Cvejic, Ana, Soranzo, Nicole, Ouwehand, Willem H., Stunnenburg, Hendrik G., Frontini, Mattia and Rendon, Augusto (2014) Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345 (6204). ISSN 1095-9203

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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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 18 Jan 2016 14:00
Last Modified: 07 Jul 2020 23:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/56426
DOI: 10.1126/science.1251033

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