Hematopoietic stem cells (HSC) are the only cells in the blood-forming
tissues that can give rise to all blood cell types and that can self-
renew to produce more HSC. In mouse and human, HSC represent up to 0.0
5% of cells in the bone marrow. HSC are almost entirely responsible fo
r the radioprotective and short- and long-term reconstituting effects
observed after bone marrow transplantation. The subsets of HSC that gi
ve rise to short-term vs long-term multilineage reconstitution can be
separated by phenotype, demonstrating that the fates of HSC are intrin
sically determined. Here we review the ontogeny and biology of HSC, th
eir expression of fate-determining genes, and the clinical importance
of HSC for transplantation and gene therapy.