Piwi reduction in the aged niche eliminates germline stem cells via Toll-GSK3 signaling.
Animals
Argonaute Proteins
/ genetics
Cadherins
/ metabolism
Cellular Senescence
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ genetics
Female
Gene Silencing
Germ Cells
/ metabolism
Glycogen Synthase Kinase 3
/ metabolism
Ovary
/ cytology
Retroelements
/ genetics
Signal Transduction
Stem Cell Niche
/ physiology
Stem Cells
/ metabolism
Toll-Like Receptors
/ metabolism
beta Catenin
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 06 2020
19 06 2020
Historique:
received:
20
05
2019
accepted:
30
05
2020
entrez:
21
6
2020
pubmed:
21
6
2020
medline:
29
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32561720
doi: 10.1038/s41467-020-16858-6
pii: 10.1038/s41467-020-16858-6
pmc: PMC7305233
doi:
Substances chimiques
Argonaute Proteins
0
Cadherins
0
Drosophila Proteins
0
Retroelements
0
Toll-Like Receptors
0
beta Catenin
0
piwi protein, Drosophila
0
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3147Références
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