Biomechanical forces promote embryonic haematopoiesis

Abstract

Following initiation of the heartbeat in vertebrate embryos, cells lining the aorta, the placental vessels and the umbilical and vitelline arteries begin to form haematopoietic cells. It has been suggested that biomechanical forces imposed on the vascular wall by the heartbeat, which sets up vascular flow and wall shear stress, could be the cue for the production of these early blood cells. Working with mouse embryonic stem cells differentiated in vitro and in mouse embryos, Adamo et al. show that exposure to fluid shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers both in vitro and in vivo. The confirmation of a link between the initiation of vascular flow and embryonic blood cell development provides new pointers for research on the production of haematopoietic progenitors for possible use in stem-cell-based therapies. Following initiation of the heartbeat in vertebrate embryos, cells lining the aorta, the placental vessels, and the umbilical and vitelline arteries begin to form haematopoietic cells. Here it is shown that biochemical forces imposed on the vascular wall at this developmental stage strongly influence development of early blood cells and that abrogation of nitric oxide—a mediator of shear-stress-induced signalling—compromises haematopoietic potential in vitro and in vivo. 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 factor Runx1 (refs 3–5), 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 differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in 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 potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.