Genesis of hematopoietic stem cells in vitro and in vivo: new insights into developmental maturation.

Hematopoietic stem cells first arise in the mammalian embryo in a primitive state, not capable of reconstituting hematopoiesis in irradiated adult recipients. As development proceeds, these cells eventually mature to acquire definitive, adult characteristics, including adult reconstitution ability. Mouse embryonic stem cells induced to undergo hematopoiesis in vitro readily generate primitive hematopoietic stem cells but rarely generate the definitive type. Recent work has stimulated a new appreciation of the events involved in the developmental maturation of hematopoietic stem cells. Application of this knowledge to in vitro differentiation systems will be critical to the successful development of hematopoietic therapies from embryonic stem cells.