Biomechanical forces promote embryonic haematopoiesis.
Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. 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 cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. 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 cells, 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 signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Luigi
L
Adamo
Olaia
O
Naveiras
Pamela L
PL
Wenzel
Shannon
S
McKinney-Freeman
Peter J
PJ
Mack
Jorge
J
Gracia-Sancho
Astrid
A
Suchy-Dicey
Momoko
M
Yoshimoto
M William
MW
Lensch
Mervin C
MC
Yoder
Guillermo
G
García-Cardeña
George Q
GQ
Daley
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D053595:Embryonic Stem Cells; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology; D011247:Pregnancy; D013314:Stress, Mechanical
D050676:Core Binding Factor Alpha 2 Subunit; D045462:Endothelium-Dependent Relaxing Factors; C493726:Runx1 protein, mouse; D009569:Nitric Oxide