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.