RRC ID 60782
Author Lin KY, Wang WD, Lin CH, Rastegari E, Su YH, Chang YT, Liao YF, Chang YC, Pi H, Yu BY, Chen SH, Lin CY, Lu MY, Su TY, Tzou FY, Chan CC, Hsu HJ.
Title Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling.
Journal Nat Commun
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.
Volume 11(1)
Pages 3147
Published 2020-6-19
DOI 10.1038/s41467-020-16858-6
PII 10.1038/s41467-020-16858-6
PMID 32561720
PMC PMC7305233
MeSH Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism* Cadherins / metabolism Cellular Senescence* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Female Gene Silencing Germ Cells / metabolism* Glycogen Synthase Kinase 3 / metabolism Ovary / cytology Ovary / metabolism Retroelements / genetics Signal Transduction Stem Cell Niche / physiology Stem Cells / metabolism Toll-Like Receptors / metabolism beta Catenin / metabolism
IF 12.121
Times Cited 0