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A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691849/ https://www.ncbi.nlm.nih.gov/pubmed/36929025 http://dx.doi.org/10.1093/procel/pwac057 |
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author | Huang, Daoyuan Zuo, Yuesheng Zhang, Chen Sun, Guoqiang Jing, Ying Lei, Jinghui Ma, Shuai Sun, Shuhui Lu, Huifen Cai, Yusheng Zhang, Weiqi Gao, Fei Peng Xiang, Andy Belmonte, Juan Carlos Izpisua Liu, Guang-Hui Qu, Jing Wang, Si |
author_facet | Huang, Daoyuan Zuo, Yuesheng Zhang, Chen Sun, Guoqiang Jing, Ying Lei, Jinghui Ma, Shuai Sun, Shuhui Lu, Huifen Cai, Yusheng Zhang, Weiqi Gao, Fei Peng Xiang, Andy Belmonte, Juan Carlos Izpisua Liu, Guang-Hui Qu, Jing Wang, Si |
author_sort | Huang, Daoyuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10691849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-106918492023-12-02 A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis Huang, Daoyuan Zuo, Yuesheng Zhang, Chen Sun, Guoqiang Jing, Ying Lei, Jinghui Ma, Shuai Sun, Shuhui Lu, Huifen Cai, Yusheng Zhang, Weiqi Gao, Fei Peng Xiang, Andy Belmonte, Juan Carlos Izpisua Liu, Guang-Hui Qu, Jing Wang, Si Protein Cell Research Articles 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. Oxford University Press 2022-11-18 /pmc/articles/PMC10691849/ /pubmed/36929025 http://dx.doi.org/10.1093/procel/pwac057 Text en ©The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Huang, Daoyuan Zuo, Yuesheng Zhang, Chen Sun, Guoqiang Jing, Ying Lei, Jinghui Ma, Shuai Sun, Shuhui Lu, Huifen Cai, Yusheng Zhang, Weiqi Gao, Fei Peng Xiang, Andy Belmonte, Juan Carlos Izpisua Liu, Guang-Hui Qu, Jing Wang, Si A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title | A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title_full | A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title_fullStr | A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title_full_unstemmed | A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title_short | A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis |
title_sort | single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of sertoli cell homeostasis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691849/ https://www.ncbi.nlm.nih.gov/pubmed/36929025 http://dx.doi.org/10.1093/procel/pwac057 |
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