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dc.contributor.authorThambyrajah, Roshana
dc.contributor.authorMazan, Milena
dc.contributor.authorPatel, Rahima
dc.contributor.authorMoignard, V
dc.contributor.authorStefanska, Monika
dc.contributor.authorMarinopoulou, Elli
dc.contributor.authorLi, Yaoyong
dc.contributor.authorLancrin, Christophe
dc.contributor.authorClapes, T
dc.contributor.authorMöröy, T
dc.contributor.authorRobin, C
dc.contributor.authorMiller, Crispin J
dc.contributor.authorCowley, S
dc.contributor.authorGöttgens, B
dc.contributor.authorKouskoff, Valerie
dc.contributor.authorLacaud, Georges
dc.date.accessioned2016-01-12T09:47:58Zen
dc.date.available2016-01-12T09:47:58Zen
dc.date.issued2016-01en
dc.identifier.citationGFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1. 2016, 18 (1):21-32 Nat. Cell Biolen
dc.identifier.issn1476-4679en
dc.identifier.pmid26619147en
dc.identifier.doi10.1038/ncb3276en
dc.identifier.urihttp://hdl.handle.net/10541/593319en
dc.description.abstractIn 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.
dc.language.isoenen
dc.rightsArchived with thanks to Nature cell biologyen
dc.titleGFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1.en
dc.typeArticleen
dc.contributor.departmentCRUK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BXen
dc.identifier.journalNature Cell Biologyen
refterms.dateFOA2020-04-22T14:20:41Z
html.description.abstractIn 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.


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