Runx1 is required for the endothelial to hematopoietic cell transition but not thereafter
By Michael J. Chen, T. Yokomizo, Brandon M. Zeigler, E. Dzierzak, N. Speck. Nature, 2009
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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.
Subfields: Cell Biology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d6dd157ac949a6a948fdea8d3dfe4aa178d74e12
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Citations in the corpus
- Tissue-Resident Macrophage Ontogeny and Homeostasis. (2016, background): “…because Runx1 expression is necessary for progenitor cells to emerge from the hemogenic endothelium, but decreases rapidly after their emergence (Chen et al., 2009), activation of labeling occurs only during a short time window, reducing the risk of tagging preceding waves and allowing a…”
- Hematopoietic stem cells derive directly from aortic endothelium during development (2010, positive): “These results complement previous studies in the avian 21 , amphibian 22 , and mammalian embryo 1 , 2 , 7 and suggest that the cellular mechanisms of HSC generation have been highly conserved across vertebrate evolution.”