Biomechanical forces promote embryonic haematopoiesis

Biomechanical forces arc emerging as critical regulators of embryo-genesis, particularly in the developing cardiovascular system^1,2. After initiation of the heart beat in vertebrates, cells lining the vent-ral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells ⁴. It remains unknown whether the biomechanical forces imposed on the vascular wall at this devel-opmental stage act as a determinant of haematopoietic potential⁶. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41⁺c-Kit⁺ haematopoietic progenitor cells⁷, concomitantly aug-menting 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 potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.