Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres.
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.
Siegl-Cachedenier
Irene
I
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain.
Flores
Ignacio
I
Klatt
Peter
P
Blasco
Maria A
MA
D000818:Animals; D049628:Body Size; D049109:Cell Proliferation; D002470:Cell Survival; D043171:Chromosomal Instability; D018859:Hair Follicle / Q000166:cytology / Q000201:enzymology* / Q000473:pathology*; D019650:Hematopoietic Stem Cell Mobilization; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D008136:Longevity; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D035781:Siblings; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000473:pathology*; D019098:Telomerase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
C422952:telomerase RNA; D012313:RNA; D019098:Telomerase