{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:05:30Z","timestamp":1791932730811,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    It remains unknown about molecular mechanisms underlying the transition of somatic cells into male germ cells. It is observed that\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    transcript is upregulated during reprogramming of Sertoli cells into human spermatogonial stem cells (SSCs) by overexpressing\n                    <jats:italic>DAZ<\/jats:italic>\n                    family genes. Significantly,\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    overexpression transits Sertoli cells into phenotypic and functional human SSCs with high safety. RNA sequencing shows that\n                    <jats:italic>DNMT1<\/jats:italic>\n                    is expressed at a higher level by\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    overexpression when Sertoli cells are reprogrammed to become human SSCs. Whole genome bisulfite sequencing elucidates that\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    modulates DNA methylation to reprogram Sertoli cells into human SSCs, and\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    interacts with DNMT1 in human SSCs generated from Sertoli cells. Intriguingly,\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    mutation results in the decreases in stemness maintenance of human SSCs and DNMT1 expression levels. Notably,\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    mutations are positively related to risk of non\u2010obstructive azoospermia (NOA) and male infertility. Collectively, these results implicate that\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    is sufficient and effective for reprogramming human Sertoli cells to SSCs through modulating DNMT1 and\n                    <jats:italic>RAD21L1<\/jats:italic>\n                    mutations leads to NOA. This study is of particular significance because it provides a novel molecular mechanism that reprograms human somatic cells into human SSCs and it could offer invaluable gametes for treating male infertility.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417491","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:06:18Z","timestamp":1760601978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>RAD21L1<\/i>\n                    Is Sufficient and Effective for Reprogramming Human Sertoli Cells to Phenotypic Spermatogonial Stem Cells Through DNA Methylation and Essential for Male Fertility"],"prefix":"10.1002","volume":"12","author":[{"given":"Caimei","family":"He","sequence":"first","affiliation":[{"name":"Hainan Academy of Sciences, School of Life Sciences and Medical Technology Hainan Medical University 352 Yehai Road, Longhua Distr Haikou 571199 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 Hunan Normal University School of Medicine  Changsha 410013 China"},{"name":"The Affiliated Hosptial of Hunan University Xiangtan Central Hospital Xiangtan 411100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province Engineering Research Center of Reproduction and Translational Medicine of Hunan Province Hunan Normal University School of Medicine  Changsha 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province Engineering Research Center of Reproduction and Translational Medicine of Hunan Province Hunan Normal University School of Medicine  Changsha 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyun","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province Engineering Research Center of Reproduction and Translational Medicine of Hunan Province Hunan Normal University School of Medicine  Changsha 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-9350","authenticated-orcid":false,"given":"Zuping","family":"He","sequence":"additional","affiliation":[{"name":"Hainan Academy of Sciences, School of Life Sciences and Medical Technology Hainan Medical University 352 Yehai Road, Longhua Distr Haikou 571199 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 Hunan Normal University 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