HEMATOPOIETIC STEM-CELLS IN THE MOUSE EMBRYONIC YOLK-SAC

The yolk sac is the first site of hematopoiesis during mammalian devel opment. The yolk sac is also the first site of blood vessel developmen t. Development of the blood islands in the yolk sac is an integrated p rocess in which these two developmental events, hematopoiesis and vasc ulogenesis, proceed in concert. This review focuses on mouse yolk sac hematopoietic stem cells (YS-HSC), describing their differentiation in vitro and in vivo. YS-HSC go through a progressive series of changes prior to the initiation of lineage-specific differentiation. Experimen ts tracing their origins from postulated hemangioblasts, and the subse quent interaction between these stem cells and yolk sac endothelial ce lls are described. Differences between the extraembryonic YS-HSC and H SC found later within the embryo, perinatally or in adults, are descri bed, YS-HSC have greater reproductive capability than HSC obtained fro m fetal liver, umbilical cord blood or adult bone marrow; they do not yet express major histocompatibility complex-associated antigens and t hey are able to reconstitute adult immunocompromised animals even,when introduced in small numbers (<100 cells/mouse). With recent results d emonstrating the feasibility of expanding YS-ASC in vitro as wed as of introducing new genes into these cells by transfection, the YS-HSC sh ows promise both as a means of achieving- long-term restitution of hem atopoiesis across histocompatibility barriers and as a self-renewing v ehicle for gene transfer.