DEFINITIVE HEMATOPOIESIS IS AUTONOMOUSLY INITIATED BY THE AGM REGION

The adult hematopoietic system of mammals is a dynamic hierarchy of ce lls with the hematopoietic stem cell at its foundation. During embryon ic development, the source and expansion potential of this cell remain unclear. Two sites of hematopoietic activity, the yolk sac and aorta- gonad-mesonephros (AGM) region, function in mouse ontogeny at the pre- liver stage of hematopoiesis. However, cellular interchange between th ese tissues obscures the embryonic site of hematopoietic stem cell gen eration. Here we present the results of a novel in vitro organ culture system demonstrating that, at day 10 in gestation, hematopoietic stem cells initiate autonomously and exclusively within the AGM region. Fu rthermore, we provide evidence for the in vitro expansion of hematopoi etic stem cells within the AGM region. These results strongly suggest that the AGM region is the source of the definitive adult hematopoieti c system, which subsequently colonizes the liver.