Embryonic origin of human hematopoiesis

Hematopoietic stem cells (HSC) are at the origin of the adult hematopoietic system. They 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 potential clinical importance in transplantation, recent research has focused on the developmental origins of embryonic HSC. During development in vertebrate embryos, two independent anatomical sites generate hematopoietic cells. The yolk sac is responsible for a first ephemeral hematopoiesis, characterized by the early appearance of hematopoietic progenitors with limited development ability that rapidly differentiate toward erythro-myeloid lineages. Self-renewing, multipotent adult-type HSC that also exhibit B and T lymphoid potentials emerge autonomously in the aorta/gonad/mesonephros (AGM) region inside the embryo. In this review, we provide a brief summary of recent developments regarding the origins of hematopoietic stem cells in the early human embryo. The recent discovery that angiotensin-converting enzyme (ACE) is a novel cell surface marker of human HSC is discussed in detail.