| RRC ID |
86091
|
| 著者 |
Mohri Y, Nie J, Morinaga H, Kato T, Aoto T, Yamanashi T, Nanba D, Matsumura H, Kirino S, Kobiyama K, Ishii KJ, Hayashi M, Suzuki T, Namiki T, Seita J, Nishimura EK.
|
| タイトル |
Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma.
|
| ジャーナル |
Nat Cell Biol
|
| Abstract |
The exposome, an individual's lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes, including hair greying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive pathways, depending on the type of genotoxic damage incurred. McSC fate tracking in mice revealed that McSCs undergo cellular senescence-coupled differentiation (seno-differentiation) in response to DNA double-strand breaks, resulting in their selective depletion and hair greying, and effectively protecting against melanoma. Conversely, carcinogens can suppress McSC seno-differentiation, even in cells harbouring double-strand breaks, by activating arachidonic acid metabolism and the niche-derived KIT ligand, thereby promoting McSC self-renewal. Collectively, the fate of individual stem cell clones-expansion versus exhaustion-cumulatively and antagonistically governs ageing phenotypes through interaction with the niche.
|
| 巻・号 |
27(10)
|
| ページ |
1647-1659
|
| 公開日 |
2025-10-1
|
| DOI |
10.1038/s41556-025-01769-9
|
| PII |
10.1038/s41556-025-01769-9
|
| PMID |
41053225
|
| MeSH |
Animals
Cell Differentiation
Cell Lineage
Cell Self Renewal
Cellular Senescence
DNA Breaks, Double-Stranded
Hair Color* / genetics
Melanocytes* / drug effects
Melanocytes* / metabolism
Melanocytes* / pathology
Melanoma* / genetics
Melanoma* / metabolism
Melanoma* / pathology
Mice
Mice, Inbred C57BL
Skin Neoplasms* / genetics
Skin Neoplasms* / metabolism
Skin Neoplasms* / pathology
Stem Cell Niche
Stem Cells* / drug effects
Stem Cells* / metabolism
Stem Cells* / pathology
|
| IF |
20.042
|
| リソース情報 |
| 加齢マウス |
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