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

doi:10.1038/s41467-020-16858-6

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^*

^*此作品的通信作者

生物醫學系(含學士班、臨床試驗與評估碩士班)

研究成果: 期刊稿件 › 文章 › 同行評審

16 引文斯高帕斯（Scopus）

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
卷	11
發行號	1
DOIs	https://doi.org/10.1038/s41467-020-16858-6
出版狀態	已出版 - 01 12 2020

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Publisher Copyright:
© 2020, The Author(s).

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10.1038/s41467-020-16858-6

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Lin, K. Y., Wang, W. D., Lin, C. H., Rastegari, E., Su, Y. H., Chang, Y. T., Liao, Y. F., Chang, Y. C., Pi, H., Yu, B. Y., Chen, S. H., Lin, C. Y., Lu, M. Y., Su, T. Y., Tzou, F. Y., Chan, C. C., & Hsu, H. J. (2020). Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling. Nature Communications, 11(1), 文章 3147. https://doi.org/10.1038/s41467-020-16858-6

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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.",

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AU - Chang, Yu Tzu

AU - Liao, Yung Feng

AU - Chang, Yi Chieh

AU - Pi, Haiwei

AU - Yu, Bo Yi

AU - Chen, Shu Hwa

AU - Lin, Chung Yen

AU - Lu, Mei Yeh

AU - Su, Tsu Yi

AU - Tzou, Fei Yang

AU - Chan, Chih Chiang

AU - Hsu, Hwei Jan

PY - 2020/12/1

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N2 - 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.

AB - 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.

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

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