{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:35Z","timestamp":1789549715780,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371546"],"award-info":[{"award-number":["32371546"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Spermatogenesis is a highly unique and intricate process, finely regulated at multiple levels, including post\u2010transcriptional regulation. N6\u2010methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, plays a significant role in transcriptional regulation during spermatogenesis. Previous research indicated extensive m6A modification at each stage of spermatogenesis, but depletion of <jats:italic>Mettl3<\/jats:italic> and\/or <jats:italic>Mettl14<\/jats:italic> in spermatogenic cells with <jats:italic>Stra8\u2010Cre<\/jats:italic> did not reveal any detectable abnormalities up to the stage of elongating spermatids. This suggests the involvement of other methyltransferases in the regulation of m6A modification during spermatogonial differentiation and meiosis. As a METTL3\/14\u2010independent m6A methyltransferase, METTL16 remains insufficiently studied in its roles during spermatogenesis. We report that male mice with <jats:italic>Mettl16<\/jats:italic><jats:sup><jats:italic>vasa\u2010cre<\/jats:italic><\/jats:sup> exhibited significantly smaller testes, accompanied by a progressive loss of spermatogonia after birth. Additionally, the deletion of <jats:italic>Mettl16<\/jats:italic> in A1 spermatogonia using <jats:italic>Stra8\u2010Cre<\/jats:italic> results in a blockade in spermatogonial differentiation. Given YTHDC1's specific recognition for METTL16 target genes, we further investigated the role of YTHDC1 using <jats:italic>Ythdc1\u2010sKO<\/jats:italic> mouse model. Our results indicate that <jats:italic>Ythdc1<\/jats:italic><jats:sup><jats:italic>Stra8\u2010cre<\/jats:italic><\/jats:sup> also impairs spermatogonial differentiation, similar to the effects observed in <jats:italic>Mettl16<\/jats:italic><jats:sup><jats:italic>Stra8\u2010cre<\/jats:italic><\/jats:sup> mice. RNA\u2010seq and m6A\u2010seq analyses revealed that deletion of either <jats:italic>Mettl6<\/jats:italic> or <jats:italic>Ythdc1<\/jats:italic> disrupted the gene expression related to chromosome organisation and segregation, ultimately leading to male infertility. Collectively, this study underscores the essential roles of the m6A writer METTL16 and its reader YTHDC1 in the differentiation of spermatogonia.<\/jats:p>","DOI":"10.1111\/cpr.13782","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T07:40:34Z","timestamp":1732952434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>METTL16<\/scp> and <scp>YTHDC1<\/scp> Regulate Spermatogonial Differentiation via <scp>m6A<\/scp>"],"prefix":"10.1111","volume":"58","author":[{"given":"Xueying","family":"Gu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing Medical University  Nanjing 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