Intraembryonic, but not yolk sac hematopoietic precursors, isolated beforecirculation, provide long-term multilineage reconstitution

The relative contribution of yolk sac and intraembryonic precursors to hema topoiesis has been a matter of long-standing controversy. As reconstitution activity has so far only been found in embryonic tissues after the onset o f circulation, the origin of reconstituting cells could not be formally est ablished. Here, we separated yolk sac and intraembryonic splanchnopleura pr ior to circulation and maintained the explants in organ culture before tran sfer. Precursors derived from the intraembryonic site generated multilineag e hematopoietic progeny in adult mice for more than 6 months. Yolk sac cell s only provided myeloid short-term reconstitution. The results reveal a dif ferential hematopoietic capacity of precirculation embryonic tissues in viv o, and indicate that the only cells capable of adult long-term hematopoiesi s are of intraembryonic origin.