GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1

Thambyrajah, R. et al. (2016) GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1. Nature Cell Biology, 18(1), pp. 21-32. (doi: 10.1038/ncb3276) (PMID:26619147)

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In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta–gonad–mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothelial-to-haematopoietic transition (EHT). Here, we establish the absolute requirement of the transcriptional repressors GFI1 and GFI1B (growth factor independence 1 and 1B) in this unique trans-differentiation process. We first demonstrate that Gfi1 expression specifically defines the rare population of HE that generates emerging HSCs. We further establish that in the absence of GFI1 proteins, HSCs and haematopoietic progenitor cells are not produced in the AGM, revealing the critical requirement for GFI1 proteins in intra-embryonic EHT. Finally, we demonstrate that GFI1 proteins recruit the chromatin-modifying protein LSD1, a member of the CoREST repressive complex, to epigenetically silence the endothelial program in HE and allow the emergence of blood cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Miller, Professor Crispin
Authors: Thambyrajah, R., Mazan, M., Patel, R., Moignard, V., Stefanska, M., Marinopoulou, E., Li, Y., Lancrin, C., Clapes, T., Möröy, T., Robin, C., Miller, C., Cowley, S., Göttgens, B., Kouskoff, V., and Lacaud, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Cell Biology
Publisher:Nature Research
ISSN (Online):1476-4679
Published Online:30 November 2015
Copyright Holders:Copyright © 2015, Springer Nature
First Published:First published in Nature Cell Biology 2016
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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