@article{ad63356629e9441eb5d33dad3a4fc36d,
title = "Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling",
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.",
author = "Lin, {Kun Yang} and Wang, {Wen Der} and Lin, {Chi Hung} and Elham Rastegari and Su, {Yu Han} and Chang, {Yu Tzu} and Liao, {Yung Feng} and Chang, {Yi Chieh} and Haiwei Pi and Yu, {Bo Yi} and Chen, {Shu Hwa} and Lin, {Chung Yen} and Lu, {Mei Yeh} and Su, {Tsu Yi} and Tzou, {Fei Yang} and Chan, {Chih Chiang} and Hsu, {Hwei Jan}",
note = "Funding Information: We thank J.T. Dubnau, A.A. Aravin, V.A. Gvozdev, M.C. Siomi, D. Godt, H. Lin, P. Jin, the Bloomington Drosophila Stock Center, NIG-FLY, the VDRC Stock Center, and the DSHB for Drosophila stocks and antibodies. We also thank the Taiwan fly core for ordering fly lines and reagents, core facilities in the Institute of Molecular Biology, the Institute of Biomedical Science and the Institute of Cellular and Organismic Biology, as well as the NGS High-Throughput Genomics core at the Biodiversity Research Center, Academia Sinica for assistance with cell isolation, image analysis and genomic sequencing, Marcus Calkins for English editing; Chung, B.-C., Huang, F., and Tsai, M,-T. for valuable comments on this article. This work was supported by a thematic grant of Academia Sinica. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-16858-6",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}