Biomechanical forces promote embryonic haematopoiesis

• Published in: Nature (London) Vol. 459; no. 7250; pp. 1131 - 1135
• Main Authors: Wenzel, Pamela L, Yoder, Mervin C, Naveiras, Olaia, Lensch, M. William, Daley, George Q, McKinney-Freeman, Shannon, García-Cardeña, Guillermo, Mack, Peter J, Suchy-Dicey, Astrid, Gracia-Sancho, Jorge, Yoshimoto, Momoko, Adamo, Luigi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.06.2009; Nature Publishing Group
• Subjects: Animals; Aorta - cytology; Aorta - embryology; Biological and medical sciences; Biomechanics; Cell Differentiation; Cell Line; Cells, Cultured; Core Binding Factor Alpha 2 Subunit - genetics; Developmental stages; Embryology: invertebrates and vertebrates. Teratology; Embryonic development; Embryonic growth stage; Embryonic Stem Cells; Embryos; Endothelium-Dependent Relaxing Factors - pharmacology; Female; Fluid dynamics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Developmental; Genetic engineering; Gonads; Hematopoiesis; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Humanities and Social Sciences; Influence; letter; Methods; Mice; multidisciplinary; Nitric oxide; Nitric Oxide - pharmacology; Organogenesis. Fetal development; Organogenesis. Physiological fonctions; Pregnancy; Rodents; Science; Science (multidisciplinary); Shear stress; Stem cells; Stress, Mechanical; Velocity; United States; Biomechanics; Embryonic development; Vertebrata; Embryo; Mammalia; Mouse; Hematopoiesis; Stem cell; Rodentia; Shear stress; Circulatory system; Progenitor cell
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature08073

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.