{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:17:29Z","timestamp":1790572649398,"version":"4.1.0"},"reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats: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 the first 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\u2019 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.<\/jats:p>","DOI":"10.1093\/procel\/pwac057","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T13:19:18Z","timestamp":1668777558000},"source":"Crossref","is-referenced-by-count":32,"title":["A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis"],"prefix":"10.1007","author":[{"given":"Daoyuan","family":"Huang","sequence":"first","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuesheng","family":"Zuo","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"},{"name":"CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"China National Center for Bioinformation , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Fifth People\u2019s Hospital of Chongqing , Chongqing 400062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Lei","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifen","family":"Lu","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"},{"name":"CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"},{"name":"China National Center for Bioinformation , Beijing 100101, China"},{"name":"Sino-Danish College, University of Chinese Academy of Sciences , Beijing 101408, China"},{"name":"Sino-Danish Center for Education and Research , Beijing 101408, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Peng","family":"Xiang","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education , Sun Yat-sen University, Guangzhou 510000, China"},{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Izpisua Belmonte","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla , CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049, China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China"},{"name":"Institute for Stem cell and Regeneration, CAS , Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Wang","sequence":"additional","affiliation":[{"name":"Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center , Xuanwu Hospital, Capital Medical University, Beijing 100053, China"},{"name":"The Fifth People\u2019s Hospital of Chongqing , Chongqing 400062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,18]]},"container-title":["Protein &amp; Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article-pdf\/doi\/10.1093\/procel\/pwac057\/47124419\/pwac057.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article-pdf\/doi\/10.1093\/procel\/pwac057\/47124419\/pwac057.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T15:37:58Z","timestamp":1672760278000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article\/doi\/10.1093\/procel\/pwac057\/6833135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/procel\/pwac057","relation":{},"ISSN":["1674-800X","1674-8018"],"issn-type":[{"value":"1674-800X","type":"print"},{"value":"1674-8018","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]},"article-number":"pwac057"}}