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 and Hwei-Jan Hsu ()
Additional contact information
Kun-Yang Lin: Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica
Wen- Der Wang: National Chiayi University
Chi-Hung Lin: Institute of Cellular and Organismic Biology, Academia Sinica
Elham Rastegari: Institute of Cellular and Organismic Biology, Academia Sinica
Yu-Han Su: Institute of Cellular and Organismic Biology, Academia Sinica
Yu-Tzu Chang: Institute of Cellular and Organismic Biology, Academia Sinica
Yung-Feng Liao: Institute of Cellular and Organismic Biology, Academia Sinica
Yi-Chieh Chang: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kweishan
Haiwei Pi: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kweishan
Bo-Yi Yu: Institute of Information Science, Academia Sinica
Shu-Hwa Chen: Institute of Information Science, Academia Sinica
Chung-Yen Lin: Institute of Information Science, Academia Sinica
Mei-Yeh Lu: Biodiversity Research Center, Academia Sinica
Tsu-Yi Su: Graduate Institute of Physiology, College of Medicine, National Taiwan University
Fei-Yang Tzou: Graduate Institute of Physiology, College of Medicine, National Taiwan University
Chih-Chiang Chan: Graduate Institute of Physiology, College of Medicine, National Taiwan University
Hwei-Jan Hsu: Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16858-6

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