GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment.

Abstract:

:Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream effectors remain largely unknown. Here, we report the identification of Gfi1 and Gfi1b as direct targets of RUNX1 and critical regulators of EHT. GFI1 and GFI1B are able to trigger, in the absence of RUNX1, the down-regulation of endothelial markers and the formation of round cells, a morphologic change characteristic of EHT. Conversely, blood progenitors in Gfi1- and Gfi1b-deficient embryos maintain the expression of endothelial genes. Moreover, those cells are not released from the yolk sac and disseminated into embryonic tissues. Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium.

journal_name

Blood

journal_title

Blood

authors

Lancrin C,Mazan M,Stefanska M,Patel R,Lichtinger M,Costa G,Vargel O,Wilson NK,Möröy T,Bonifer C,Göttgens B,Kouskoff V,Lacaud G

doi

10.1182/blood-2011-10-386094

subject

Has Abstract

pub_date

2012-07-12 00:00:00

pages

314-22

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2011-10-386094

journal_volume

120

pub_type

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