GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment.
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.
Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.
Christophe
C
Lancrin
Milena
M
Mazan
Monika
M
Stefanska
Rahima
R
Patel
Monika
M
Lichtinger
Guilherme
G
Costa
Ozge
O
Vargel
Nicola K
NK
Wilson
Tarik
T
Möröy
Constanze
C
Bonifer
Berthold
B
Göttgens
Valerie
V
Kouskoff
Georges
G
Lacaud
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055018:Hemangioblasts / Q000166:cytology* / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015017:Yolk Sac / Q000166:cytology / Q000196:embryology / Q000502:physiology
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; C486395:Gfi1b protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors