Distinct classes of human stem cells that differ in proliferative and self-renewal potential

The composition of the human hematopoietic stem cell compartment is poorly understood due to the absence of experimental tools with which to character ize the developmental program of individual stem cells. We report here that human stem cells differ markedly in their repopulation capacity and self-r enewal potential, as determined using nonobese diabetic-severe combined imm unodeficiency (NOD-SCID) mice transplanted with retrovirally transduced cor d blood stem cells, called SCID-repopulating cells (SRCs). Clonal stem cell analysis based on the identification of unique retroviral integration site s within serial bone marrow aspirates showed that repopulation was generall y oligoclonal with extensive variability in the lifespan and proliferative capacity of individual SRCs. Most clones contributed to human cell engraftm ent for several weeks after transplantation and then disappeared but others appeared later and persisted. Further evidence for stem cell heterogeneity was found in the secondary transplantation capacity of SRCs. These data po int to the existence of different classes of human stem cells with variable self-renewal potential and short- or long-term repopulating capacity.