The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets

Abstract

Hematopoietic stem cells (HSCs) display extensive heterogeneity in their behavior even when isolated as phenotypically homogeneous populations. It is not clear whether this heterogeneity reflects inherently diverse subsets of HSCs or a homogeneous population of HSCs diversified by their response to different external stimuli. To address this, we analyzed 97 individual HSCs in long-term transplantation assays. HSC clones were obtained from unseparated bone marrow (BM) through limiting dilution approaches. Following transplantation into individual hosts, donor-type cells in blood were measured bimonthly and the resulting repopulation kinetics were grouped according to overall shape. Only 16 types of repopulation kinetics were found among the HSC clones even though combinatorially 54 groups were possible. All HSC clones, regardless of their origin, could be assigned to this subset of groups, and the probability of finding new patterns is negligible. Thus, the full repertoire of repopulating HSCs was covered. These data indicate that the HSC compartment consists of a limited number of distinct HSC subsets, each with predictable behavior. Enrichment of HSCs (Lin^–Rho^–SP) changes the representation of HSC types by selecting for distinct subsets of HSCs. These data from the steady-state HSC repertoire could provide a basis for the diagnosis of perturbed patterns of HSCs potentially caused by disease or aging.