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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number3147
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

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

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