西亚试剂：Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells

发布时间：2025-07-04

Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation

Ken Inomata1,2,3,Takahiro Aoto1,4,Nguyen Thanh Binh1,Natsuko Okamoto1,5,Shintaro Tanimura1,3,Tomohiko Wakayama6,Shoichi Iseki6,Eiji Hara7,Takuji Masunaga2,Hiroshi Shimizu3andEmi K. Nishimura1,4,,

1 Division of Stem Cell Medicine, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-0934, Japan
2 Fundamental Research Laboratories, KOSé Corporation, 1-18-4 Azusawa, Itabashi-ku, Tokyo 174-0051, Japan
3 Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan
4 Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan
5 Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-Ku, Kyoto, 606-8507, Japan
6 Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan
7 Division of Cancer Biology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6, Ariake, Koto-ku, Tokyo 135-8550, Japan

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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