{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T09:02:54Z","timestamp":1781427774574,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008608","name":"Sumitomo Foundation","doi-asserted-by":"publisher","award":["190421"],"award-info":[{"award-number":["190421"]}],"id":[{"id":"10.13039\/100008608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16H06280"],"award-info":[{"award-number":["JP16H06280"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In male mammals, spermatogonial stem cells (SSCs) are essential for sustaining lifelong spermatogenesis within the testicular open niche, a unique environment that allows SSC migration over an extended niche area. As SSCs undergo continuous mitotic division, mutations accumulate and are transmitted to the descendant SSC clones. Therefore, SSC clonal fate behaviors, in terms of their efficiencies in completing spermatogenesis and undergoing expansion within the niche, influence sperm genomic diversity. We aimed to elucidate the effects of physiological aging on SSC clonal fate behavior within the testicular open niche. We used single\u2010cell RNA sequencing, lineage tracing, and intravital live imaging to investigate SSC behavior in aged mouse testes, where spermatogenesis, although reduced, persists. We found that undifferentiated spermatogonia maintained gene expression heterogeneity during aging. Among these, GFR\u03b11\n                    <jats:sup>+<\/jats:sup>\n                    cells, which exhibited state heterogeneity, showed accelerated proliferation and persistent motility, continuing to function as SSCs in older mice. In contrast, a subset of SSCs characterized by low\n                    <jats:italic>Egr4<\/jats:italic>\n                    and\n                    <jats:italic>Cops5<\/jats:italic>\n                    expression did not contribute to spermatid formation. These non\u2013sperm\u2010forming SSC clones increased in proportion among the total SSC clones and expanded spatially within the testicular open niche in old mice, a phenomenon not observed in young mice. The expansion of non\u2013sperm\u2010forming SSC clones in aged testes suggests that they occupy a niche space, limiting the availability of functional SSCs and potentially reducing sperm production and genetic diversity. These findings highlight age\u2010specific clonal characteristics as hallmarks of stem cell aging within the testicular open niche and provide novel insights into the mechanisms governing reproductive aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70019","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T12:08:41Z","timestamp":1740226121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Age\u2010Dependent Clonal Expansion of Non\u2013Sperm\u2010Forming Spermatogonial Stem Cells in Mouse Testes"],"prefix":"10.1111","volume":"24","author":[{"given":"Terumichi","family":"Kawahara","sequence":"first","affiliation":[{"name":"Graduate School of Agricultural Science Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Germ Cell Biology, National Institute for Basic Biology National Institutes of Natural Sciences  Okazaki Japan"},{"name":"Graduate Institute for Advanced Studies, SOKENDAI  Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Germ Cell Biology, National Institute for Basic Biology National Institutes of Natural Sciences  Okazaki Japan"},{"name":"Graduate Institute for Advanced Studies, SOKENDAI  Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kamo","sequence":"additional","affiliation":[{"name":"Graduate School of Agricultural Science Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Kanouchi","sequence":"additional","affiliation":[{"name":"Graduate School of Agricultural Science Tohoku University  Sendai 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