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Hematopoietic stem cells engraft in mice with absolute efficiency

Abstract

The engraftment of murine hematopoietic stem cells (HSCs) into irradiated mice is thought to be an inefficient process, but has yet to be measured directly. We used two independent strategies to test their engraftment efficiency: one measured competition of unpurified donor bone marrow cells with recipient cells in murine hosts and the other tracked the engraftment of one highly purified stem cell injected per recipient. The results showed that stem cells engrafted with near absolute efficiency. Thus, inefficient engraftment cannot explain the low frequency of permanent reconstitutions observed with pure HSC fractions and instead suggests most initially engrafted cells fail to sustain self-renewal.

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Figure 1: Experimental strategy for measurement of the engraftment efficiency of unpurified HSCs in irradiated mice.
Figure 2: Isolation of RholoLy6A+Kit+B220CD3 cells.
Figure 3: Short- and long-term erythroid reconstitution by RholoLy6A+Kit+B220CD3 cells in KitW–41J/W–41J hosts.
Figure 4: Multipotentiality of single RholoLy6A+Kit+B220CD3 cells.

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Acknowledgements

We thank J. Till for productive discussions of stochastic clonal evolution. Supported by operating grants to N.N.I. from the Canadian Institutes of Health Research and the National Cancer Institute of Canada.

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Correspondence to Norman N. Iscove.

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Benveniste, P., Cantin, C., Hyam, D. et al. Hematopoietic stem cells engraft in mice with absolute efficiency. Nat Immunol 4, 708–713 (2003). https://doi.org/10.1038/ni940

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