Distinct classes of human stem cells that differ in proliferative and
self-renewal potential
Guillermo Guenechea1, 2, 3, Olga I. Gan1, 3, Craig Dorrell1, 3
& John E. Dick1
1
Programs in Cancer/Blood Research and Gene Therapy,
Hospital for Sick Children and Department of Molecular and Medical Genetics,
University of Toronto, 555 University Ave. Toronto
, ON, Canada M5G 1X8.
The composition of the human hematopoietic stem cell compartment is poorly
understood due to the absence of experimental tools with which to characterize
the developmental program of individual stem cells. We report here that human
stem cells differ markedly in their repopulation capacity and self-renewal
potential, as determined using nonobese diabetic−severe combined immunodeficiency
(NOD-SCID) mice transplanted with retrovirally transduced cord blood stem
cells, called SCID-repopulating cells (SRCs). Clonal stem cell analysis based
on the identification of unique retroviral integration sites within serial
bone marrow aspirates showed that repopulation was generally oligoclonal with
extensive variability in the lifespan and proliferative capacity of individual
SRCs. Most clones contributed to human cell engraftment 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 point to the existence of different classes of
human stem cells with variable self-renewal potential and short- or long-term
repopulating capacity.
