A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.

IF 13.6 1区 生物学 Q1 CELL BIOLOGY
Daoyuan Huang, Yuesheng Zuo, Chen Zhang, Guoqiang Sun, Ying Jing, Jinghui Lei, Shuai Ma, Shuhui Sun, Huifen Lu, Yusheng Cai, Weiqi Zhang, Fei Gao, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang
{"title":"A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.","authors":"Daoyuan Huang, Yuesheng Zuo, Chen Zhang, Guoqiang Sun, Ying Jing, Jinghui Lei, Shuai Ma, Shuhui Sun, Huifen Lu, Yusheng Cai, Weiqi Zhang, Fei Gao, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang","doi":"10.1093/procel/pwac057","DOIUrl":null,"url":null,"abstract":"<p><p>The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"888-907"},"PeriodicalIF":13.6000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691849/pdf/","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein & Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/procel/pwac057","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 6

Abstract

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

灵长类动物睾丸衰老的单核转录组图谱揭示了精原干细胞储存库的衰竭和支持细胞稳态的丧失。
睾丸是男性生殖的关键,随着年龄的增长,其功能的逐渐下降与不孕症有关。然而,灵长类动物睾丸衰老的调控机制在很大程度上仍然难以捉摸。在这里,我们通过建立一个单核转录组图谱来解决灵长类动物睾丸衰老相关的细胞和分子改变。沿着精子发生轨迹的基因表达模式揭示了与精子干细胞库消耗、减数分裂紊乱和精子发生受损相关的分子程序。值得注意的是,Sertoli细胞被认为是最容易衰老的细胞类型,因为它与年龄相关的转录谱受到严重干扰。同时,对支持细胞稳态至关重要的转录因子Wilms' Tumor 1 (WT1)的下调与细胞衰老加速、紧密连接中断和细胞身份特征受损有关,这些都可能有助于为精子发生创造一个不利的微环境。总的来说,我们的研究在单细胞分辨率下深入描述了非人类灵长类动物(NHP)睾丸衰老的转录组特征,为睾丸衰老和与年龄相关的男性生殖疾病的治疗干预提供了潜在的诊断生物标志物和靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Protein & Cell
Protein & Cell CELL BIOLOGY-
CiteScore
24.00
自引率
0.90%
发文量
1029
审稿时长
6-12 weeks
期刊介绍: Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信