Origin of Hematopoietic Stem Cells in Embryonic Development

Abstract

Bone marrow is the main hematopoietic organ of mature mammals. Hematopoietic stem cells (HSCs) are maintained in it throughout an organism’s whole life; it also regulates the production of mature blood cells. Adult HSCs are characterized by polypotency, self-renewal, and a specific phenotype, as well as by the ability to direct migration to the hematopoietic organs. The ability of the HSCs to restore hematopoiesis after transplantation into another organism is the main functional criterion for their existence in tissue. However, HSCs, which function in postnatal ontogenesis and possess these properties, represent the final stage of maturation of their precursors (pre-HSCs), which arise in prenatal development. In embryogenesis, hematopoiesis occurs in several transitional blood-forming organs: the yolk sac, aorta-gonad-mesonephros (AGM), placenta, and liver. Despite the long history of research on hematopoietic system ontogenesis, the anatomical site of the origination of the first pre-HSCs, which give rise to the definitive HSC line, is still not entirely clear. The review summarizes modern concepts of the features of the hematopoietic cells formed in the yolk sac, AGM, and placenta, and their contribution to embryonic liver colonization and in definitive hematopoiesis. Further study of the mechanisms of HSC formation in embryogenesis is of undoubted importance, not only for an understanding of the fundamental aspects of hematopoietic system functioning but also for improvement in treatment methods for hematological diseases.