Review article Stem cell heterogeneity: implications for aging and regenerative medicine

For decades, hematopoietic stem cells (HSCs) were thought to be a homoge-neous population of cells with flexible behavior. Now a new picture has emerged: The HSC compartment consists of sev-eral subpopulations of HSCs each with distinct, preprogrammed differentiation and proliferation behaviors. These pro-grams are epigenetically fixed and are stably bequeathed to all daughter HSCs on self-renewal. HSCs within each subset are remarkably similar in their self-renewal and differentiation behaviors, to the point where their life span can be predicted with mathematical certainty. Three subsets can be distinguished when HSCs are classified by their differentia-tion capacity: myeloid-biased, balanced, and lymphoid-biased HSCs. The relative number of the HSC subsets is develop-mentally regulated. Lymphoid-biased HSCs are found predominantly early in the life of an organism, whereas myeloid-biased HSCs accumulate in aged mice and humans. Thus, the discovery of dis-tinct subpopulations of HSCs has led to a new understanding of HCS aging. This finding has implications for other aspects of HSC biology and applications in re-generative medicine. The possibility that other adult tissue stem cells show similar heterogeneity and mechanisms of aging is discussed. (Blood. 2012;119(17): 3900-3907