• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

DOS-3 介导细胞非自主性 DAF-16/FOXO 活性，拮抗线虫生殖干细胞/祖细胞衰老相关的损耗。

DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells.

机构信息

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

出版信息

Nat Commun. 2024 Jun 8;15(1):4904. doi: 10.1038/s41467-024-49318-6.

DOI:10.1038/s41467-024-49318-6
PMID:38851828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11162419/
Abstract

Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.

摘要

年龄相关的干细胞耗竭导致组织退化和组织再生失败，从而导致机体水平的衰老。先前我们报道了在秀丽隐杆线虫中，一种非细胞自主的 DAF-16/FOXO 活性拮抗生殖干细胞/祖细胞（GSPCs）的年龄相关丢失，表明干细胞衰老的调节发生在器官系统水平。在这里，我们通过进行组织特异性 DAF-16/FOXO 转录组分析，发现了将非细胞自主的 DAF-16/FOXO 活性与 GSPC 维持联系起来的分子效应子。我们的数据表明，dos-3 编码一种非典型的 Notch 配体，是 DAF-16/FOXO 的直接转录靶标，并通过在生殖系中激活 Notch 信号转导，介导非细胞自主的 DAF-16/FOXO 活性对 GSPC 维持的影响。重要的是，人同源蛋白的表达可以在这种情况下替代 DOS-3 发挥功能。由于 Notch 信号转导控制着许多组织干细胞的特化，类似的机制可能存在于其他衰老的干细胞系统中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/61972fc956b6/41467_2024_49318_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/848bbf440086/41467_2024_49318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/49dbd9a75b30/41467_2024_49318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/8b38e3263a68/41467_2024_49318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/e3bc6e3af4d8/41467_2024_49318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/0f7f72a1c072/41467_2024_49318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/61972fc956b6/41467_2024_49318_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/848bbf440086/41467_2024_49318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/49dbd9a75b30/41467_2024_49318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/8b38e3263a68/41467_2024_49318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/e3bc6e3af4d8/41467_2024_49318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/0f7f72a1c072/41467_2024_49318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7616/11162419/61972fc956b6/41467_2024_49318_Fig6_HTML.jpg

相似文献

1
DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells.DOS-3 介导细胞非自主性 DAF-16/FOXO 活性，拮抗线虫生殖干细胞/祖细胞衰老相关的损耗。
Nat Commun. 2024 Jun 8;15(1):4904. doi: 10.1038/s41467-024-49318-6.
2
Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells.非自主性DAF-16/FOXO活性拮抗秀丽隐杆线虫生殖系干细胞/祖细胞与衰老相关的损失。
Nat Commun. 2015 May 11;6:7107. doi: 10.1038/ncomms8107.
3
Non-autonomous insulin signaling delays mitotic progression in C. elegans germline stem and progenitor cells.非自主性胰岛素信号传导会延迟秀丽隐杆线虫生殖系干细胞和祖细胞的有丝分裂进程。
PLoS Genet. 2024 Dec 23;20(12):e1011351. doi: 10.1371/journal.pgen.1011351. eCollection 2024 Dec.
4
C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.秀丽隐杆线虫的DAF-16/FOXO与转化生长因子-β/骨形态发生蛋白（TGF-β/BMP）信号传导相互作用，通过激活mTORC1诱导生殖系肿瘤形成。
PLoS Genet. 2017 May 26;13(5):e1006801. doi: 10.1371/journal.pgen.1006801. eCollection 2017 May.
5
Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.线虫 FOXO/DAF-16 向干细胞的非细胞自主信号传导。
PLoS Genet. 2012;8(8):e1002836. doi: 10.1371/journal.pgen.1002836. Epub 2012 Aug 16.
6
The protein kinase MBK-1 contributes to lifespan extension in mutant and germline-deficient .蛋白激酶MBK-1有助于延长突变体和生殖系缺陷型的寿命。
Aging (Albany NY). 2017 May 25;9(5):1414-1432. doi: 10.18632/aging.101244.
7
Insulin signaling promotes germline proliferation in C. elegans.胰岛素信号促进秀丽隐杆线虫生殖系的增殖。
Development. 2010 Feb;137(4):671-80. doi: 10.1242/dev.042523.
8
Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.通过对秀丽隐杆线虫异构体特异性 daf-16/FoxO 突变体的综合分析揭示长寿基因。
Genetics. 2015 Oct;201(2):613-29. doi: 10.1534/genetics.115.177998. Epub 2015 Jul 27.
9
The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators.秀丽隐杆线虫成年神经元胰岛素/胰岛素样生长因子信号通路/叉头转录因子O亚家族转录组揭示成年表型调控因子。
Nature. 2016 Jan 7;529(7584):92-6. doi: 10.1038/nature16483. Epub 2015 Dec 14.
10
Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity.秀丽隐杆线虫的EAK-3通过对核DAF-16/FoxO活性的非自主调节来抑制滞育。
Dev Biol. 2008 Mar 15;315(2):290-302. doi: 10.1016/j.ydbio.2007.12.032. Epub 2008 Jan 3.

引用本文的文献

1
Non-autonomy of age-related morphological changes in the germline stem cell niche.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
bioRxiv. 2025 Jun 16:2025.06.13.658151. doi: 10.1101/2025.06.13.658151.

本文引用的文献

1
ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells.ATM 信号调节减数分裂前期和增殖细胞中的黏连蛋白行为。
Nat Struct Mol Biol. 2023 Apr;30(4):436-450. doi: 10.1038/s41594-023-00929-5. Epub 2023 Mar 6.
2
Hallmarks of aging: An expanding universe.衰老的特征：一个不断扩大的领域。
Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3.
3
Germline Stem and Progenitor Cell Aging in .生殖系干细胞和祖细胞衰老于…… （原文此处不完整）
Front Cell Dev Biol. 2021 Jul 8;9:699671. doi: 10.3389/fcell.2021.699671. eCollection 2021.
4
GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1.GLP-1 Notch-LAG-1 CSL 通过转录靶标 lst-1 和 sygl-1 来控制生殖干细胞命运。
PLoS Genet. 2020 Mar 20;16(3):e1008650. doi: 10.1371/journal.pgen.1008650. eCollection 2020 Mar.
5
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.Metascape 为系统水平数据集的分析提供了面向生物学家的资源。
Nat Commun. 2019 Apr 3;10(1):1523. doi: 10.1038/s41467-019-09234-6.
6
Rapid population-wide declines in stem cell number and activity during reproductive aging in .生殖衰老过程中， 大量干细胞数量和活性的迅速下降。
Development. 2019 Apr 23;146(8):dev173195. doi: 10.1242/dev.173195.
7
The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms.印记基因 Delta 样非经典 Notch 配体 1（Dlk1）在哺乳动物中保守存在，通过 Notch 依赖和非依赖机制在组织发育和再生过程中发挥生长调节作用。
Cytokine Growth Factor Rev. 2019 Apr;46:17-27. doi: 10.1016/j.cytogfr.2019.03.006. Epub 2019 Mar 23.
8
Notch and Stem Cells.Notch 与干细胞。
Adv Exp Med Biol. 2018;1066:235-263. doi: 10.1007/978-3-319-89512-3_12.
9
SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans.SYGL-1和LST-1将龛信号传导与PUF RNA抑制相联系，以维持秀丽隐杆线虫的干细胞。
PLoS Genet. 2017 Dec 12;13(12):e1007121. doi: 10.1371/journal.pgen.1007121. eCollection 2017 Dec.
10
GLP-1/Notch activates transcription in a probability gradient across the germline stem cell pool.GLP-1/Notch在整个生殖系干细胞库中以概率梯度激活转录。
Elife. 2016 Oct 5;5:e18370. doi: 10.7554/eLife.18370.