Transcriptional diversity during lineage commitment of human blood progenitors
Authors
Chen, Lu
Kostadima, Myrto
Martens, Joost HA
Canu, Giovanni
Garcia, Sara P
Macaulay, Iain C
Bielczyk-Maczynska, Ewa
Coe, Sophia
Farrow, Samantha
Poudel, Pawan
Burden, Frances
Jansen, Sjoert BG
Attwood, Antony
Bariana, Tadbir
de, Bono Bernard
Breschi, Alessandra
Chambers, John C
BRIDGE, Consortium
Choudry, Fizzah A
Clarke, Laura
Coupland, Paul
van, der Ent Martijn
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 HD
Kooner, Jaspal S
Laffan, Michael
Lentaigne, Claire
Labalette, Charlotte
Martin, Tiphaine
Meacham, Stuart
Mumford, Andrew
Nürnberg, Sylvia
Palumbo, Emilio
van, der Reijden Bert A
Richardson, David
Slodkowicz, Greg
Tamuri, Asif U
Vasquez, Louella
Voss, Katrin
Watt, Stephen
Westbury, Sarah
Flicek, Paul
Loos, Remco
Goldman, Nick
Stunnenberg, Hendrik G
Publication Date
2014-09-26Journal Title
Science
ISSN
0036-8075
Publisher
AAAS
Volume
345
Pages
12510331-125103310
Language
en_US
Type
Article
Metadata
Show full item recordCitation
Chen, L., Kostadima, M., Martens, J. H., Canu, G., Garcia, S. P., Turro Bassols, E., Downes, K., et al. (2014). Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345 12510331-125103310. https://doi.org/10.1126/science.1251033
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 identify extensive cell-type specific expression changes: 6,711 genes and 10,724 transcripts, enriched in non-protein coding elements at early stages of differentiation. In addition, we discovered 7,881 novel splice junctions and 2,301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrate experimentally cell specific isoform usage, identifying 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.
Sponsorship
Wellcome Trust (082961/Z/07/Z)
Wellcome Trust (084183/Z/07/Z)
British Heart Foundation (RG/09/012/28096)
NIHR�Central Commissioning Facility (CCF) (RP-PG-0310-1002)
MRC (MR/K024043/1)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (091310/Z/10/Z)
Identifiers
External DOI: https://doi.org/10.1126/science.1251033
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246350
Rights
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