title: Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.
abstract: Haematopoietic stem cells (HSCs) are the founder cells of the adult haematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative haematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus-the aorta, vitelline and umbilical arteries, yolk sac and placenta. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters and that Runx1 functions during the transition from 'haemogenic endothelium' to HSCs. Here we show by conditional deletion that Runx1 activity in vascular-endothelial-cadherin-positive endothelial cells is indeed essential for intra-arterial cluster, haematopoietic progenitor and HSC formation in mice. In contrast, Runx1 is not required in cells expressing Vav1, one of the first pan-haematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for haematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chen
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Zeigler
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D050676:Core Binding Factor Alpha 2 Subunit; D051567:Proto-Oncogene Proteins c-vav; D000099152:Cadherin 5; C493726:Runx1 protein, mouse; C496619:Vav1 protein, mouse