Exhaustion of stem cells is a hallmark of aging. In the testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expressing the differentiation factor () in spermatogonia while lineage-labeling these cells. Strikingly, blocking -lineage dedifferentiation under normal conditions in virgin males has no impact on the GSC pool. However, in mated males or challenging conditions, inhibiting -lineage dedifferentiation markedly reduces the number of GSCs and their ability to proliferate and differentiate. We find that -lineage derived GSCs have significantly higher proliferation rates than sibling GSCs in the same testis. We determined that Jun N-terminal kinase (JNK) activity is autonomously required for -lineage dedifferentiation. Overall, we show that dedifferentiation provides a mechanism to maintain the germline and ensure fertility under chronically stressful conditions.
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| http://dx.doi.org/10.7554/eLife.36095 | DOI Listing |
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