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

被引：304

作者：

Inomata, Ken ^{[1
,2
,3
]}

Aoto, Takahiro ^{[1
,4
]}

Binh, Nguyen Thanh ^{[1
]}

Okamoto, Natsuko ^{[1
,5
]}

Tanimura, Shintaro ^{[1
,3
]}

Wakayama, Tomohiko ^{[6
]}

Iseki, Shoichi ^{[6
]}

Hara, Eiji ^{[7
]}

Masunaga, Takuji ^{[2
]}

Shimizu, Hiroshi ^{[3
]}

Nishimura, Emi K. ^{[1
,4
]}

机构：

[1] Kanazawa Univ, Div Stem Cell Med, Ctr Canc & Stem Cell Res, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan

[2] KOSE Corp, Fundamental Res Labs, Itabashi Ku, Tokyo 1740051, Japan

[3] Hokkaido Univ, Dept Dermatol, Grad Sch Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan

[4] Tokyo Med & Dent Univ, Dept Stem Cell Biol, Med Res Inst, Chiyoda Ku, Tokyo 1010062, Japan

[5] Kyoto Univ, Dept Dermatol, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan

[6] Kanazawa Univ, Dept Histol & Embryol, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan

[7] Japanese Fdn Canc Res, Div Canc Biol, Inst Canc, Koto Ku, Tokyo 1358550, Japan

来源：

CELL | 2009年 / 137卷 / 06期

关键词：

DNA-DAMAGE; IONIZING-RADIATION; CELLULAR SENESCENCE; ATAXIA-TELANGIECTASIA; TUMOR SUPPRESSION; MICE DEFICIENT; CYCLE ARREST; ATM; MOUSE; PHENOTYPES;

D O I：

10.1016/j.cell.2009.03.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1088 / 1099

页数：12

共 59 条

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EFFECT OF X-IRRADIATION ON DIFFERENTIATING HAIR FOLLICLES [J].