Publication Date:
2009-01-09
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744041/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744041/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Michael J -- Yokomizo, Tomomasa -- Zeigler, Brandon M -- Dzierzak, Elaine -- Speck, Nancy A -- CA23108/CA/NCI NIH HHS/ -- R01 CA058343/CA/NCI NIH HHS/ -- R01DK54077/DK/NIDDK NIH HHS/ -- R01HL091724/HL/NHLBI NIH HHS/ -- R37 DK054077/DK/NIDDK NIH HHS/ -- R37 DK054077-09/DK/NIDDK NIH HHS/ -- T32 AI-07519/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):887-91. doi: 10.1038/nature07619. Epub 2009 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129762" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/metabolism
;
Cadherins/metabolism
;
*Cell Differentiation
;
Core Binding Factor Alpha 2 Subunit/genetics/*metabolism
;
Endothelial Cells/*cytology
;
Female
;
*Gene Expression Regulation, Developmental
;
Hematopoietic Stem Cells/*cytology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Proto-Oncogene Proteins c-vav/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
