Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling

Kun Yang Lin, Wen Der Wang, Chi Hung Lin, Elham Rastegari, Yu Han Su, Yu Tzu Chang, Yung Feng Liao, Yi Chieh Chang, Haiwei Pi, Bo Yi Yu, Shu Hwa Chen, Chung Yen Lin, Mei Yeh Lu, Tsu Yi Su, Fei Yang Tzou, Chih Chiang Chan, Hwei Jan Hsu

研究成果: 雜誌貢獻文章同行評審

摘要

Transposons are known to participate in tissue aging, but their effects on aged stem cells remain unclear. Here, we report that in the Drosophila ovarian germline stem cell (GSC) niche, aging-related reductions in expression of Piwi (a transposon silencer) derepress retrotransposons and cause GSC loss. Suppression of Piwi expression in the young niche mimics the aged niche, causing retrotransposon depression and coincident activation of Toll-mediated signaling, which promotes Glycogen synthase kinase 3 activity to degrade β-catenin. Disruption of β-catenin-E-cadherin-mediated GSC anchorage then results in GSC loss. Knocking down gypsy (a highly active retrotransposon) or toll, or inhibiting reverse transcription in the piwi-deficient niche, suppresses GSK3 activity and β-catenin degradation, restoring GSC-niche attachment. This retrotransposon-mediated impairment of aged stem cell maintenance may have relevance in many tissues, and could represent a viable therapeutic target for aging-related tissue degeneration.

原文英語
文章編號3147
期刊Nature Communications
11
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2020
對外發佈Yes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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