Biomechanical forces promote embryonic haematopoiesis

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Abstract

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system1 2. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factorRunx1(refs3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential6. Here, using mouse embryonic stem cells differentiatedin vitro, we show that fluid shear stress increases the expression ofRunx1in CD41+c-Kit+ haematopoietic progenitor cells7, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling8, compromises haematopoietic potentialin vitroandin vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.

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