Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, National Chung Hsing University and Academia Sinica, Taipei, 11529, Taiwan.
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, 40227, Taiwan.
Nat Commun. 2020 Jun 19;11(1):3147. doi: 10.1038/s41467-020-16858-6.
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.
转座子已知参与组织衰老，但它们对衰老干细胞的影响尚不清楚。在这里，我们报告在果蝇卵巢生殖干细胞（GSC）巢中，与衰老相关的 Piwi（转座子沉默子）表达减少会解除反转录转座子的抑制，导致 GSC 丧失。在年轻的巢中抑制 Piwi 的表达模拟了衰老的巢，导致反转录转座子的抑制和 Toll 介导的信号的偶发激活，这促进糖原合酶激酶 3 活性降解 β-连环蛋白。随后破坏β-连环蛋白-E-钙黏蛋白介导的 GSC 固定会导致 GSC 丧失。在 piwi 缺陷的巢中敲低 gypsy（一种高度活跃的反转录转座子）或 toll，或抑制逆转录，可抑制 GSK3 活性和 β-连环蛋白降解，恢复 GSC-巢附着。这种反转录转座子介导的衰老干细胞维持损伤可能与许多组织有关，并且可能成为与衰老相关的组织退化的可行治疗靶点。
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