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Transcriptional diversity during lineage commitment of human blood progenitors

Chen, L; Kostadima, M; Martens, JHA; Canu, G; Garcia, SP; Turro, E; Downes, K; ... Rendon, A; + view all (2014) Transcriptional diversity during lineage commitment of human blood progenitors. Science , 345 (6204) , Article 1251033. 10.1126/science.1251033. Green open access

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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.

Type: Article
Title: Transcriptional diversity during lineage commitment of human blood progenitors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.1251033
Publisher version: https://doi.org/10.1126/science.1251033
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10093617
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