Biomechanical forces promote embryonic haematopoiesis

Luigi Adamo, Olaia Naveiras, Pamela L. Wenzel, Shannon McKinney-Freeman, Peter J. Mack, Jorge Gracia-Sancho, Astrid Suchy-Dicey, Momoko Yoshimoto, M. William Lensch, Mervin C. Yoder, Guillermo Garcia-Cardeña, George Q. Daley

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Abstract

Biomechanical forces arc emerging as critical regulators of embryo-genesis, particularly in the developing cardiovascular system1,2. 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.

Original languageEnglish (US)
Pages (from-to)1131-1135
Number of pages5
JournalNature
Volume459
Issue number7250
DOIs
StatePublished - Jun 25 2009

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Adamo, L., Naveiras, O., Wenzel, P. L., McKinney-Freeman, S., Mack, P. J., Gracia-Sancho, J., Suchy-Dicey, A., Yoshimoto, M., Lensch, M. W., Yoder, M. C., Garcia-Cardeña, G., & Daley, G. Q. (2009). Biomechanical forces promote embryonic haematopoiesis. Nature, 459(7250), 1131-1135. https://doi.org/10.1038/nature08073