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bioRxiv · 10.1101/2025.06.13.658151

Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche

Gupta, N.·Sinks, M.·Hubbard, E. J. A.
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Abstract

Declines in tissue renewal and repair due to alterations in tissue stem cells is a hallmark of aging. Many stem cell pools are maintained morphologically complex niches. Using the C. elegans hermaphrodite germline stem cell system, we analyzed age-related changes in the morphology of the niche, the distal tip cell (DTC), and identified a molecular mechanism that promotes a subset of these changes. We found decreases in the number and length of long DTC processes with age. We also found that a long-lived daf-2 mutant exhibits a daf-16-dependent maintenance of long DTC processes. Surprisingly, the tissue requirement for daf-16(+) is non-autonomous, and daf-16(+) in body wall muscle is both necessary and sufficient. In addition, after a delay, pre-formed DTC processes deteriorate upon premature germline differentiation, but not upon cell cycle inhibition. We propose a reciprocal DTC-germline interaction model and speculate how reduced daf-2 activity both delays stem cell exhaustion and maintains DTC processes. These studies establish the C. elegans DTC as a powerful in vivo model for understanding age-related changes in cellular morphology and their consequences in stem cell systems. SUMMARYThe C. elegans germline stem cell niche morphology is markedly altered with age and is regulated non-autonomously from the muscle by insulin/IGF-like signaling. Results suggest reciprocal niche-germline regulation.

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Gupta, N., Sinks, M., Hubbard, E. J. A.. 2025-06-16. Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche. https://doi.org/10.1101/2025.06.13.658151

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