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^*

^*Corresponding author for this work

Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Research output: Contribution to journal › Journal Article › peer-review

17 Scopus citations

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 language	English
Article number	3147
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16858-6
State	Published - 01 12 2020

Bibliographical note

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

Access to Document

10.1038/s41467-020-16858-6

Cite this

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), Article 3147. https://doi.org/10.1038/s41467-020-16858-6

@article{2dcc122d39014947897989b757695acb,

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 = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-16858-6",

language = "英语",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling

AU - Lin, Kun Yang

AU - Wang, Wen Der

AU - Lin, Chi Hung

AU - Rastegari, Elham

AU - Su, Yu Han

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

Y1 - 2020/12/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85086744763&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16858-6

DO - 10.1038/s41467-020-16858-6

M3 - 文章

C2 - 32561720

AN - SCOPUS:85086744763

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3147

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this