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Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells

Nature Medicine volume 9, pages 369–371 (2003)Cite this article

To the editor

Hematopoietic stem cells (HSCs) can be serially transplanted only 4–6 times in mice before long-term multi-lineage reconstitution is no longer observed in the recipient animal1, fueling speculation that HSCs, like other types of somatic cells, may have limited replicative potential. Telomere shortening is the sole factor limiting the replicative capacity of a number of normal human somatic cells grown in vitro, as over-expression of telomerase reverse transcriptase (TERT) in these cells stabilizes telomere length and allows indefinite growth2. Although telomeres do shorten during HSC division in humans3 and mice4 despite detectable levels of telomerase activity in these cells5, it is not known whether stabilization of telomere length is sufficient to sustain indefinite transplantation capacity. We developed a transgenic mouse strain in which mouse TERT is over-expressed in HSCs and assessed the effect on telomere length and transplantation capacity of HSCs during serial transplantation.

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Figure 1: Analysis of telomere length and replicative capacity during serial transplantation of HSCs in mice transgenic for mouse TERT under the control of the H–2Kb promoter.

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Acknowledgements

We thank L. Harrington for critical reading of the manuscript and M. Gilbert and L. Jerabek for technical assistance. All experiments were approved by the Institutional Animal Care and Use Committee and the Administrative Panel on Laboratory Animal Care at Stanford University. I.L.W. was supported by National Institutes of Health grants CA 42551 and DK 53074; R.C.A. was supported by National Research Service Award/NIH post-doctoral fellowship CA76708 and an Irvington Institute of Immunology fellowship.

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Authors and Affiliations

  1. Pathology Department, Beckman Center, Stanford University School of Medicine, Stanford University, Stanford, California, USA

    Richard C. Allsopp & Irving L. Weissman

  2. Geron Corporation, Menlo Park, California, USA

    Gregg B. Morin & Calvin B. Harley

  3. Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts, USA

    James W. Horner & Ronald DePinho

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  1. Richard C. Allsopp
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  2. Gregg B. Morin
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  3. James W. Horner
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  4. Ronald DePinho
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  5. Calvin B. Harley
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  6. Irving L. Weissman
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Correspondence to Richard C. Allsopp.

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G.B.M. was a recent, and C.B.H. is a present full-time employee of Geron Corporation, an organization that could gain or lose financially through publication of this work.

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Allsopp, R., Morin, G., Horner, J. et al. Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med 9, 369–371 (2003). https://doi.org/10.1038/nm0403-369

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