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生殖系干细胞微环境中与年龄相关的形态变化的非自主性

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

作者信息

Gupta Nilay, Sinks Mia, Hubbard E Jane Albert

机构信息

Department Biology, New York University.

Department of Cell Biology, NYU Grossman School of Medicine.

出版信息

bioRxiv. 2025 Jun 16:2025.06.13.658151. doi: 10.1101/2025.06.13.658151.

DOI:10.1101/2025.06.13.658151
PMID:40667375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12262334/
Abstract

A decline in tissue renewal and repair due to changes in tissue stem cells is a hallmark of aging. Many stem cell pools are maintained by interaction with morphologically complex local niches. Using the 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 that a long-lived mutant exhibits a -dependent decline in number and length of long DTC processes. Surprisingly, the tissue requirement for is non-autonomous and is independent of the longevity requirement: in body wall muscle is both necessary and sufficient. We also determined that pre-formed DTC processes deteriorate prematurely when the underlying germline differentiates. We propose a reciprocal DTC-germline interaction model and speculate a mechanism by which reducing activity prevents stem cell exhaustion. These studies establish the DTC as a powerful model for understanding age-related changes in cellular morphology and their consequences in stem cell systems.

摘要

由于组织干细胞的变化导致组织更新和修复能力下降是衰老的一个标志。许多干细胞库通过与形态复杂的局部微环境相互作用来维持。利用雌雄同体生殖系干细胞系统,我们分析了微环境(远端顶端细胞,DTC)形态的年龄相关变化,并确定了促进这些变化子集的分子机制。我们发现,一个长寿突变体表现出依赖于的长DTC突起数量和长度的下降。令人惊讶的是,组织对的需求是非自主的,并且独立于长寿需求:体壁肌肉中的是必要且充分的。我们还确定,当潜在的生殖系分化时,预先形成的DTC突起会过早退化。我们提出了一种相互的DTC-生殖系相互作用模型,并推测了一种降低活性可防止干细胞耗竭的机制。这些研究将DTC确立为理解细胞形态年龄相关变化及其在干细胞系统中的后果的强大模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/75a66f5c0979/nihpp-2025.06.13.658151v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/507ab1ff5b3a/nihpp-2025.06.13.658151v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/a3fc96f2cc5f/nihpp-2025.06.13.658151v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/78ef8ed0823e/nihpp-2025.06.13.658151v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/a73c6c880d5d/nihpp-2025.06.13.658151v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/75a66f5c0979/nihpp-2025.06.13.658151v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/507ab1ff5b3a/nihpp-2025.06.13.658151v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/a3fc96f2cc5f/nihpp-2025.06.13.658151v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/78ef8ed0823e/nihpp-2025.06.13.658151v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/a73c6c880d5d/nihpp-2025.06.13.658151v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4d/12262334/75a66f5c0979/nihpp-2025.06.13.658151v1-f0005.jpg

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A role for organ level dynamics in morphogenesis of the C. elegans hermaphrodite distal tip cell.器官水平动力学在秀丽隐杆线虫雌雄同体远端细胞形态发生中的作用。
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DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells.
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Nat Commun. 2024 Jun 8;15(1):4904. doi: 10.1038/s41467-024-49318-6.
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A DTC morphometrics package for quantification of complex and variable cellular morphology using ImageJ.一种用于使用ImageJ对复杂且多变的细胞形态进行量化的DTC形态测量软件包。
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Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity.衰老破坏生殖干细胞的时空调节和巢位完整性。
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