Siegl-Cachedenier Irene, Flores Ignacio, Klatt Peter, Blasco Maria A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid, E-28029, Spain.
J Cell Biol. 2007 Oct 22;179(2):277-90. doi: 10.1083/jcb.200704141.
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.
器官稳态和机体存活与干细胞维持组织再生的能力相关。由于端粒酶缩短加速,端粒酶缺陷小鼠表现出组织再生缺陷和过早死亡。这表明端粒长度和端粒酶活性对干细胞生物学有直接影响。我们最近发现,短端粒会损害表皮干细胞从毛囊生态位中迁出的能力,导致皮肤和毛发的生长受损,并抑制体外表皮干细胞的增殖能力。在此,我们证明,在端粒极短的小鼠中重新引入端粒酶足以纠正表皮毛囊干细胞缺陷。此外,将端粒酶重新引入这些小鼠可通过在不增加肿瘤发生的情况下预防退行性病变,从而使其寿命正常。