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.

journal_name

Nat Commun

journal_title

Nature communications

authors

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

doi

10.1038/s41467-020-16858-6

subject

Has Abstract

pub_date

2020-06-19 00:00:00

pages

3147

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16858-6

journal_volume

11

pub_type

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