Nature 459, 1131-1135 (25 June 2009) | doi:10.1038/nature08073; Received 18 April 2008; Accepted 23 April 2009; Published online 13 May 2009

Biomechanical forces promote embryonic haematopoiesis

Luigi Adamo1,4, Olaia Naveiras2,4, Pamela L. Wenzel2, Shannon McKinney-Freeman2, Peter J. Mack1, Jorge Gracia-Sancho1, Astrid Suchy-Dicey1, Momoko Yoshimoto3, M. William Lensch2, Mervin C. Yoder3, Guillermo García-Cardeña1,4 & George Q. Daley2,4

  1. Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
  2. Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Division of Hematology, Brigham and Women's Hospital; Harvard Stem Cell Institute; Manton Center for Orphan Disease Research; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
  3. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
  4. These authors contributed equally to this work.

Correspondence to: Guillermo García-Cardeña1,4George Q. Daley2,4 Correspondence and requests for materials should be addressed to G.Q.D. (Email: george.daley@childrens.harvard.edu) or G.G.-C. (Email: guillermo_garcia-cardena@hms.harvard.edu).

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.


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