The emergence of definitive hematopoietic stem cells in the mammal

Abstract

Hematopoietic stem cells (HSC) are the basis for blood formation during adult life. The amazing potency of HSCs has been exploited for over 30 years in regenerative therapies for patients with blood-related genetic disease and leukemia. As clinically important cells and also as the most widely studied cell differentiation system, they have been the focus of intense fundamental research. Indeed, HSC research has established many paradigms in the more general field of stem cells. Recently, the study of the embryonic origins of HSCs and their genetic program is beginning to provide unique insights into how these stem cells are formed, maintained, and expanded, and how they contribute to the complex adult hematopoietic system. Although many short-lived hematopoietic progenitors are present in early stage mammalian embryos, this review will focus on the events leading to emergence of the most potent cells of the hematopoietic system, HSCs and on their developmental lineage relationships. Developmental and genetic studies further our understanding of the fate determination events occurring in several embryonic tissues leading to the generation of potent HSCs--those cells with the ability to long-term, high-level repopulate all hematopoietic lineages of the adult. Several mammalian embryonic tissues contribute to the growth and/or generation of potent HSCs that are the source of blood cells throughout the lifespan of the individual. Insight into how mammalian HSC fate is determined has been provided through functional, phenotypic, and genetic studies at early developmental stages.