Nature Immunology
- 7, 1225 - 1233 (2006)
Published online: 1 October 2006; | doi:10.1038/ni1393
Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartmentJoby L McKenzie1, 2, 3, Olga I Gan1, 3, Monica Doedens1, Jean C Y Wang1 & John E Dick1, 21
Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario M5G 1L7, Canada. 2
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 3
These authors contributed equally to this manuscript.
Correspondence should be addressed to John E Dick jdick@uhnres.utoronto.ca Hematopoiesis requires tight regulation of the hematopoietic stem cell (HSC) population; however, the dynamics of HSC use at steady state are uncertain. Over 3–7 months, we evaluated the repopulation and self-renewal of more than 600 individual human 'severe combined immunodeficiency mouse–repopulating cells' (SRCs), tracked on the basis of lentiviral integration sites, in serially transplanted immune-deficient mice, as well as of SRC daughter cells that migrated to different marrow locations in a single mouse. Our data demonstrate maintenance by self-renewing SRCs after an initial period of clonal instability, a result inconsistent with the clonal succession model. We found wide variation in proliferation kinetics and self-renewal among SRCs, as well as between SRC daughter cells that repopulated equivalently, suggesting that SRC fate is unpredictable before SRCs enter more rigid 'downstream' developmental programs.
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