Identification of the hematopoietic stem cell niche in the fetal liver

Hematopoiesis and vasculogenesis/angiogenesis are tightly linked. Here we develop a model by which the hematopoietic system titrates its stem cell activity against the angiogenesis of arterial vasculature in the fetal liver.;Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+ NG2 + progenitor cells associate with portal vessels, and form a critical niche promoting FL HSC maintenance and expansion. Nestin+ NG2 + cells and HSCs scale during development with the fractal branching patterns of portal vessels derived from the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+ NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation.