Embryonic beginnings of adult hematopoietic stem cells

Hematopoietic stem cells (HSC) are at the foundation of the adult hematopoietic system. HSC give rise to all blood cells through a complex series of proliferation and differentiation events that occur throughout the lifespan of the individual. Because of their clinical importance in transplantation protocols, recent research has focused on the developmental origins and potential of embryonic HSC. In both mammalian and non-mammalian vertebrate embryos, two independent anatomical sites have been found to generate hematopoietic cells. The yolk sac (or its equivalent in amphibians, the ventral blood islands) participates in a first transient wave of hematopoiesis by producing primitive erythrocytes. Importantly, adult-type HSCs emerge autonomously in a second wave of hematopoietic generation in an intraembryonic region surrounding the dorsal aorta, the aorta-gonads-mesonephros (AGM) region. In this review, we will discuss research advances in the field of developmental hematopoiesis, with a particular emphasis on the cellular origins of AGM HSC and their regulation by the embryonic hematopoietic microenvironment.