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Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.

Nature | Feb 12, 2009

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.

Pubmed ID: 19129762 RIS Download

Mesh terms: Animals | Antigens, CD | Cadherins | Cell Differentiation | Core Binding Factor Alpha 2 Subunit | Endothelial Cells | Female | Gene Expression Regulation, Developmental | Hematopoietic Stem Cells | Male | Mice | Mice, Inbred C57BL | Mice, Transgenic | Proto-Oncogene Proteins c-vav

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Associated grants

  • Agency: NHLBI NIH HHS, Id: R01HL091724
  • Agency: NCI NIH HHS, Id: R01 CA058343
  • Agency: NIAID NIH HHS, Id: T32 AI007519
  • Agency: NHLBI NIH HHS, Id: R01 HL091724
  • Agency: NCI NIH HHS, Id: CA23108
  • Agency: NCI NIH HHS, Id: P30 CA023108
  • Agency: NIDDK NIH HHS, Id: R01DK54077
  • Agency: NIDDK NIH HHS, Id: R37 DK054077
  • Agency: NIAID NIH HHS, Id: T32 AI-07519
  • Agency: NIDDK NIH HHS, Id: R37 DK054077-09
  • Agency: NIDDK NIH HHS, Id: R01 DK054077

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