Journal
CELL
Volume 137, Issue 6, Pages 1088-1099Publisher
CELL PRESS
DOI: 10.1016/j.cell.2009.03.037
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Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology [17689033, 19390293, 20012017]
- Uehara Memorial Foundation
- Kato Memorial Bioscience Foundation
- Grants-in-Aid for Scientific Research [17689033, 19390293, 20012017] Funding Source: KAKEN
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Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a stemness checkpoint'' to maintain the stem cell quality and quantity.
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