2025-10-06 東京大学
Web要約 の発言:
老化とがん化における幹細胞の拮抗的運命
<関連情報>
- https://www.ims.u-tokyo.ac.jp/imsut/jp/about/press/page_00356.html
- https://www.ims.u-tokyo.ac.jp/imsut/content/000011804.pdf
- https://www.nature.com/articles/s41556-025-01769-9
ストレス下での拮抗的な幹細胞の運命が、白髪と黒色腫の決定を左右する Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma
Yasuaki Mohri,Jialiang Nie,Hironobu Morinaga,Tomoki Kato,Takahiro Aoto,Takashi Yamanashi,Daisuke Nanba,Hiroyuki Matsumura,Sakura Kirino,Kouji Kobiyama,Ken J. Ishii,Masahiro Hayashi,Tamio Suzuki,Takeshi Namiki,Jun Seita & Emi K. Nishimura
Nature Cell Biology Published:06 October 2025
DOI:https://doi.org/10.1038/s41556-025-01769-9
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.
