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Biol."],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sperm development is critical for male reproductive capability; any disruption during the process of spermatogenesis will result in male infertility. In this research, we used the C\u2010Nap1 encoded by the gene of <jats:italic>Cep250<\/jats:italic> knockout mouse line as the model to evaluate the impact of absent C\u2010Nap1 on spermatogenesis. To investigate the interaction between C\u2010Nap1 and spermatogenesis, we utilized single\u2010cell RNA sequencing to analyze 10,332 <jats:italic>C\u2010Nap1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> and 13,308 <jats:italic>C\u2010Nap1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> testicular cells. We identified five main cell types within seminiferous tubules, including spermatogonia, Sertoli cells, spermatogonia stem cells, Leydig cells, and spermatocytes. We found a critical reduction in testicular spermatogonia and spermatocytes in C\u2010Nap1\u2010null testes, compared to its <jats:italic>C\u2010Nap1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> controls. By combining uniform manifold approximation and projection clustering and psedotime ordering, we distinguished five spermatogonial stages\/subtypes, demonstrating that type B spermatogonia differentiation and meiotic initiation are impaired during C\u2010Nap1\u2010null spermatogenesis. Following gene ontology enrichment analysis, meiosis\u2010specific genes downregulated in the <jats:italic>C\u2010Nap1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> testicular cells were further verified by reverse transcription polymerase chain reaction (RT\u2010PCR). Based on the differential gene expression, certain downregulated genes such as <jats:italic>Ctnnb1<\/jats:italic> and <jats:italic>Aurka<\/jats:italic> encoding C\u2010Nap1\u2010binding potential \u03b2\u2010Catenin and Aurka are encountered, which may account for defective type B spermatogonia differentiation and meiotic entry in C\u2010Nap1\u2010null testes.<\/jats:p>","DOI":"10.1002\/qub2.71","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T09:54:00Z","timestamp":1732614840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010cell analyses reveal impaired type B spermatogonia differentiation and meiotic entry in C\u2010Nap1\u2010null testes"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8385-3908","authenticated-orcid":false,"given":"Junlin","family":"Li","sequence":"first","affiliation":[{"name":"Medical School University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Zanvyl Krieger School of Arts and Sciences Johns Hopkins University  Baltimore Maryland USA"},{"name":"Viterbi School of Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liansheng","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory Guang\u2019anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntao","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute for TCM\u2010X  Beijing China"},{"name":"MOE Key Laboratory of Bioinformatics  Beijing China"},{"name":"Bioinformatics Division Department of Automation BNRist  Beijing China"},{"name":"Center for Synthetic &amp; Systems Biology Tsinghua University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical School University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(98)80109-9"},{"key":"e_1_2_11_3_1","article-title":"Regulation of spermatogonia","volume":"10","author":"Zhou Q","year":"2021","journal-title":"Int J Biomed Health Sci"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.036"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2345"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-02-0108"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.139451"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.01.011"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14038-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.754054"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202153805"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.08.022"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00410"},{"key":"e_1_2_11_15_1","article-title":"Dynamics of transcriptional programs and chromatin accessibility in mouse spermatogonial cells from early postnatal to adult life","volume":"12","author":"Lazar\u2010Contes I","year":"2023","journal-title":"Elife"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00894-z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.06.010"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki005"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00013.2015"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199799"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094291"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1596308"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab168"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac947"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"}],"container-title":["Quantitative Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/qub2.71","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T10:00:02Z","timestamp":1734948002000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/qub2.71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/qub2.71"],"URL":"https:\/\/doi.org\/10.1002\/qub2.71","archive":["Portico"],"relation":{},"ISSN":["2095-4689","2095-4697"],"issn-type":[{"type":"print","value":"2095-4689"},{"type":"electronic","value":"2095-4697"}],"subject":[],"published":{"date-parts":[[2024,11,26]]},"assertion":[{"value":"2024-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71"}}