Organ homeostasis and organismal survival are related to the ability of stem cells to sustain tissue regeneration. As a consequence of accelerated telomerase shortening, telomerase-deficient mice show defective tissue regeneration and premature death. This suggests a direct impact of telomere length and telomerase activity on stem cell biology. We recently found that short telomeres impair the ability of epidermal stem cells to mobilize out of the hair follicle (HF) niche, resulting in impaired skin and hair growth and in the suppression of epidermal stem cell proliferative capacity in vitro. Here, we demonstrate that telomerase reintroduction in mice with critically short telomeres is sufficient to correct epidermal HF stem cell defects. Additionally, telomerase reintroduction into these mice results in a normal life span by preventing degenerative pathologies in the absence of increased tumorigenesis.
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22 October 2007
Article|
October 22 2007
Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres
Irene Siegl-Cachedenier,
Irene Siegl-Cachedenier
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
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Ignacio Flores,
Ignacio Flores
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
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Peter Klatt,
Peter Klatt
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
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Maria A. Blasco
Maria A. Blasco
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
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Irene Siegl-Cachedenier
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
Ignacio Flores
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
Peter Klatt
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
Maria A. Blasco
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain
Correspondence to Maria A. Blasco: [email protected]
Abbreviations used in this paper: a.u.f., arbitrary units of fluorescence; HF, hair follicle; IFE, interfollicular epidermis; LRC, label retaining cell; MEF, mouse embryonic fibroblast; Q-FISH, quantitative FISH; TPA, 12-O-tetradecanoylphorbol- 13-acetate.
Received:
January 04 2007
Accepted:
September 25 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 179 (2): 277–290.
Article history
Received:
January 04 2007
Accepted:
September 25 2007
Citation
Irene Siegl-Cachedenier, Ignacio Flores, Peter Klatt, Maria A. Blasco; Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres . J Cell Biol 22 October 2007; 179 (2): 277–290. doi: https://doi.org/10.1083/jcb.200704141
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