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 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.
Guenechea
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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.
Gan
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Dorrell
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Dick
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D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013997:Time Factors; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
D017931:DNA Primers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins