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

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  • Kun-Yang Lin

    (Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica
    Graduate Institute of Biotechnology, National Chung Hsing University
    Institute of Cellular and Organismic Biology, 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
    Institute of Cellular and Organismic Biology, Academia Sinica
    Biotechnology Center, National Chung Hsing University)

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.

Suggested Citation

  • 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, 2020. "Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16858-6
    DOI: 10.1038/s41467-020-16858-6
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