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 Blood, 15 October 2008, Vol. 112, No. 8, pp. 3194-3204.
Prepublished online as a Blood First Edition Paper on August 6, 2008; DOI 10.1182/blood-2008-02-139055.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis

Lauren C. Goldie13, Jennifer L. Lucitti4, Mary E. Dickinson4, and Karen K. Hirschi15

1 Department of Pediatrics and 2 Center for Cell & Gene Therapy, Baylor College of Medicine, Houston, TX; 3 Agricultural Research Service (ARS) Children's Nutrition Research Center, Houston, TX; and Departments of 4 Molecular Physiology and Biophysics and 5 Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX

During developmental hematopoiesis, multilineage hematopoietic progenitors are thought to derive from a subset of vascular endothelium. Herein, we define the phenotype of such hemogenic endothelial cells and demonstrate, on a clonal level, that they exhibit multilineage hematopoietic potential. Furthermore, we have begun to define the molecular signals that regulate their development. We found that the formation of yolk sac hemogenic endothelium and its hematopoietic potential were significantly impaired in the absence of retinoic acid (RA) signaling, and could be restored in RA-deficient (Raldh2–/–) embryos by provision of exogenous RA in utero. Thus, we identify a novel, critical role for RA signaling in the development of hemogenic endothelium that contributes to definitive hematopoiesis.


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