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 placenta1,2. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters3 and that Runx1 functions during the transition from ‘haemogenic endothelium’ to HSCs4,5. 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.
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The authors thank G. Ward for his assistance with flow, K. Downs for technical advice, T. Graf for the Vav-Cre mice, and P. Huber for the Cdh5 sequences. This work was supported by R01HL091724 (N.A.S.), R01DK54077 (E.D.) and T32 AI-07519 (B.M.Z.). Core services were supported in part by the Norris Cotton Cancer Center (NIH CA23108) and the Abramson Family Cancer Research Institute.
Author Contributions T.Y. performed the experiments in Fig. 3d. B.M.Z. performed the experiments in Fig. 1b, d. M.J.C. performed all the remaining experiments. E.D. participated in the interpretation of the experiments and writing the manuscript. N.A.S. participated in the design and interpretation of the experiments, wrote the manuscript and made the figures.
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Chen, M., Yokomizo, T., Zeigler, B. et al. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 457, 887–891 (2009). https://doi.org/10.1038/nature07619
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