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- Title
Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment.
- Authors
McKenzie, Joby L; Gan, Olga I; Doedens, Monica; Wang, Jean C Y; Dick, John E
- Abstract
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.
- Publication
Nature immunology, 2006, Vol 7, Issue 11, p1225
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1393