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Nevertheless, the molecular mechanisms controlling the fate determinations of human SSCs remain elusive. In this study, we identified a selective expression of APBB1 in dormant human SSCs. We demonstrated for the first time that APBB1 interacted with KAT5, which led to the suppression of GDF15 expression and consequent inhibition of human SSC proliferation. Intriguingly, Apbb1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice assumed the disrupted spermatogenesis and markedly reduced fertility. SSC transplantation assays revealed that Apbb1 silencing enhanced SSC colonization and impeded their differentiation, which resulted in the impaired spermatogenesis. Notably, 4 deleterious\n            <jats:italic>APBB1<\/jats:italic>\n            mutation sites were identified in 2,047 patients with non-obstructive azoospermia (NOA), and patients with the c.1940C&gt;G mutation had a similar testicular phenotype with Apbb1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. Additionally, we observed lower expression levels of APBB1 in NOA patients with spermatogenic arrest than in obstructive azoospermia patients with normal spermatogenesis. Collectively, our findings highlight an essential role of APBB1\/KAT5\/GDF15 in governing human SSC fate decisions and maintaining normal spermatogenesis and underscore them as therapeutic targets for treating male infertility.\n          <\/jats:p>","DOI":"10.34133\/research.0647","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T16:56:57Z","timestamp":1741885017000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":2,"title":["Essential Regulation of Spermatogonial Stem Cell Fate Decisions and Male Fertility by APBB1 via Interaction with KAT5 and GDF15 in Humans and Mice"],"prefix":"10.34133","volume":"8","author":[{"given":"Dai","family":"Zhou","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University","place":["China"]},{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, \rCentral South University, Changsha, Hunan 410000, China."},{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province; Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Institute of Interdisciplinary Studies, Hunan Normal University, Hunan 410013, China."},{"name":"Hainan Medical University","place":["China"]},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, \rCentral South University, Changsha, Hunan 410000, China."},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, \rCentral South University, Changsha, Hunan 410000, China."},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenghui","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, \rCentral South University, Changsha, Hunan 410000, China."},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-9350","authenticated-orcid":true,"given":"Zuping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province; 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