Journal
SCIENCE
Volume 345, Issue 6204, Pages 1580-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1251033
Keywords
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Categories
Funding
- European Commission [HEALTH-F5-2011-282510]
- National Institute for Health Research (NIHR)
- British Heart Foundation [RP-PG-0310-1002, RG/09/12/28096]
- NETSIM FP7 program - European Commission
- NHS Blood and Transplant
- NIHR
- NIHR BioResource-Rare Diseases
- Wellcome Trust [WT098051, WT091310, 084183/Z/07/Z, 082961/Z/07/Z, 095908]
- EU FP7 EPIGENESYS initiative [257082]
- Cancer Research UK [C45041/A14953]
- British Heart Foundation Clinical Research Training Fellowship [FS/12/27/29405]
- Imperial College BRC
- Medical Research Council
- British Society of Haematology/NHS Blood and Transplant
- EMBL
- FWO-Vlaanderen [G.0B17.13N]
- British Heart Foundation [FS/12/27/29405, RG/09/012/28096] Funding Source: researchfish
- Cancer Research UK [14953] Funding Source: researchfish
- Medical Research Council [MR/K023489/1, MR/J011711/1, MR/K024043/1, MR/K006584/1, MC_UP_0801/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10214, RP-PG-0310-1002, NF-SI-0513-10151, ACF-2012-14-006] Funding Source: researchfish
- MRC [MR/J011711/1, MR/K023489/1, MR/K024043/1, MC_UP_0801/1] Funding Source: UKRI
- Wellcome Trust [084183/Z/07/Z, 082961/Z/07/Z] Funding Source: Wellcome Trust
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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.
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