ETV2 expression marks blood and endothelium precursors, including hemogenic endothelium, at the onset of blood development.
BACKGROUND
ETV2 has been identified as an important player in embryonic hematopoiesis. However, the cell populations in which this transcription factor is expressed and operates during blood specification remain to be fully characterized. Here we address these issues using ES cells and a transgenic mouse line expressing green fluorescent protein (GFP) under the control of ETV2 regulatory elements, allowing us to observe the tight association between ETV2 expression and the initiation of hematopoiesis.


RESULTS
Both in differentiating ES cells and gastrulating embryos ETV2::GFP is mostly found co-expressed with endothelial markers and defines a subset of cells with greatly enriched primitive erythroid potential. Upon culture ETV2::GFP cells rapidly up-regulate CD41, down-regulate endothelium cell surface markers and generate definitive hematopoietic progenitors. Altogether these characteristics represent the hallmark of hemogenic endothelium cells, a specialized endothelium originating from the hemangioblast and giving rise to hematopoietic cells. Importantly, ETV2 deficiency results in a complete absence of hemogenic endothelium in differentiating ES cells and gastrulating embryos.


CONCLUSIONS
Altogether our data reveal that ETV2 marks hemogenic endothelium in gastrulating embryos and is absolutely required for the formation of this precursor at the onset of hematopoiesis. These results enhance our understanding of embryonic hematopoiesis and the factors driving hemogenic endothelium specification.
Cancer Research UK Stem Cell Hematopoiesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Sarah
S
Wareing
Alexia
A
Eliades
Georges
G
Lacaud
Valerie
V
Kouskoff
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000378:metabolism; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000196:embryology* / Q000378:metabolism; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D055018:Hemangioblasts / Q000378:metabolism* / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019076:Transgenes; D054928:Validation Studies as Topic
D015415:Biomarkers; C503994:ER71 protein, mouse; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins