{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:27:11Z","timestamp":1790778431653,"version":"4.1.0"},"reference-count":74,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"tdm","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":"crossref","award":["32200646"],"award-info":[{"award-number":["32200646"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31725013"],"award-info":[{"award-number":["31725013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32000586"],"award-info":[{"award-number":["32000586"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31970794"],"award-info":[{"award-number":["31970794"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92268111"],"award-info":[{"award-number":["92268111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key Research and Development Program of China","award":["2022YFA0806302"],"award-info":[{"award-number":["2022YFA0806302"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFC1003500"],"award-info":[{"award-number":["2018YFC1003500"]}]},{"name":"National Key Research and Development Program of China","award":["2019YFA0801800"],"award-info":[{"award-number":["2019YFA0801800"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92268205"],"award-info":[{"award-number":["92268205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-019"],"award-info":[{"award-number":["2021-I2M-1-019"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2017-I2M-3-009"],"award-info":[{"award-number":["2017-I2M-3-009"]}]},{"name":"State Key Laboratory Special Fund","award":["2060204"],"award-info":[{"award-number":["2060204"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    In adult mammals, spermatogenesis embodies the complex developmental process from spermatogonial stem cells (SSCs) to spermatozoa. At the top of this developmental hierarchy lie a series of SSC subpopulations. Their individual identities as well as the relationships with each other, however, remain largely elusive. Using single-cell analysis and lineage tracing, we discovered both in mice and humans the quiescent adult SSC subpopulation marked specifically by forkhead box protein C2 (FOXC2). All spermatogenic progenies can be derived from FOXC2\n                    <jats:sup>+<\/jats:sup>\n                    SSCs and the ablation of FOXC2\n                    <jats:sup>+<\/jats:sup>\n                    SSCs led to the depletion of the undifferentiated spermatogonia pool. During germline regeneration, FOXC2\n                    <jats:sup>+<\/jats:sup>\n                    SSCs were activated and able to completely restore the process. Germ cell-specific\n                    <jats:italic>Foxc2<\/jats:italic>\n                    knockout resulted in an accelerated exhaustion of SSCs and eventually led to male infertility. Furthermore, FOXC2 prompts the expressions of negative regulators of cell cycle thereby ensures the SSCs reside in quiescence. Thus, this work proposes that the quiescent FOXC2\n                    <jats:sup>+<\/jats:sup>\n                    SSCs are essential for maintaining the homeostasis and regeneration of spermatogenesis in adult mammals.\n                  <\/jats:p>","DOI":"10.7554\/elife.85380","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T13:01:30Z","timestamp":1679662890000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85380","source":"Crossref","is-referenced-by-count":8,"title":["Identification of quiescent FOXC2+ spermatogonial stem cells in adult mammals"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-1703","authenticated-orcid":true,"given":"Zhipeng","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-0653","authenticated-orcid":true,"given":"Cheng","family":"Jin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyu","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jielin","family":"Tang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhuan","family":"Ou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingfeng","family":"Zou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhen","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Mang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zg1tt02","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee","place":["Dundee, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Miao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfang","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8395-9991","authenticated-orcid":true,"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.1172\/JCI75943","article-title":"PAX7 expression defines germline stem cells in the adult testis","volume":"124","author":"Aloisio","year":"2014","journal-title":"The Journal of Clinical Investigation"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1196\/annals.1392.005","article-title":"Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche","volume":"1106","author":"Arai","year":"2007","journal-title":"Annals of the New York Academy of Sciences"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"40012","DOI":"10.1074\/jbc.M205345200","article-title":"Growth retardation, polyploidy, and multinucleation induced by Clast3, a novel cell cycle-regulated protein","volume":"277","author":"Bahar","year":"2002","journal-title":"The Journal of Biological Chemistry"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1034\/j.1399-0004.2002.620608.x","article-title":"FOXC2 truncating mutation in distichiasis, lymphedema, and cleft palate","volume":"62","author":"Bahuau","year":"2002","journal-title":"Clinical Genetics"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1083\/jcb.200307056","article-title":"FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1","volume":"164","author":"Bakker","year":"2004","journal-title":"The Journal of Cell Biology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/ng1366","article-title":"Plzf is required in adult male germ cells for stem cell self-renewal","volume":"36","author":"Buaas","year":"2004","journal-title":"Nature Genetics"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrm3591","article-title":"Molecular regulation of stem cell quiescence","volume":"14","author":"Cheung","year":"2013","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1002\/aja.1001180211","article-title":"Renewal of spermatogonia in man","volume":"118","author":"Clermont","year":"1966","journal-title":"The American Journal of Anatomy"},{"key":"bib9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0015-0282(16)36120-9","article-title":"Spermatogenesis in man. A study of the spermatogonial population","volume":"17","author":"Clermont","year":"1966","journal-title":"Fertility and Sterility"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/aja.1001260106","article-title":"Two classes of spermatogonial stem cells in the monkey (Cercopithecus aethiops)","volume":"126","author":"Clermont","year":"1969","journal-title":"The American Journal of Anatomy"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/ng1367","article-title":"Essential role of Plzf in maintenance of spermatogonial stem cells","volume":"36","author":"Costoya","year":"2004","journal-title":"Nature Genetics"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"42453","DOI":"10.1074\/jbc.M402197200","article-title":"The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation","volume":"279","author":"Davis","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.1242\/dev.150284","article-title":"Spermatogonial kinetics in humans","volume":"144","author":"Di Persio","year":"2017","journal-title":"Development"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1530\/rep.1.01081","article-title":"A revised model for spermatogonial expansion in man: lessons from non-human primates","volume":"132","author":"Ehmcke","year":"2006","journal-title":"Reproduction"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/humupd\/dmk001","article-title":"Spermatogonial stem cells: questions, models and perspectives","volume":"12","author":"Ehmcke","year":"2006","journal-title":"Human Reproduction"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1210\/en.2018-01088","article-title":"Transcription factor USF1 is required for maintenance of germline stem cells in male mice","volume":"160","author":"Faisal","year":"2019","journal-title":"Endocrinology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/dvg.20310","article-title":"Generation of a germ cell-specific mouse transgenic Cre line, Vasa-Cre","volume":"45","author":"Gallardo","year":"2007","journal-title":"Genesis"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Briefings in Bioinformatics"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.neo.2014.04.004","article-title":"NHERF1\/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane","volume":"16","author":"Georgescu","year":"2014","journal-title":"Neoplasia"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/mrd.20026","article-title":"Stage-specific and tissue-specific expression characteristics of differentially expressed genes during mouse spermatogenesis","volume":"67","author":"Guo","year":"2004","journal-title":"Molecular Reproduction and Development"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The adult human testis transcriptional cell atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Research"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.stem.2014.04.006","article-title":"Chromatin and transcription transitions of mammalian adult germline stem cells and spermatogenesis","volume":"15","author":"Hammoud","year":"2014","journal-title":"Cell Stem Cell"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.stem.2014.01.019","article-title":"Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states","volume":"14","author":"Hara","year":"2014","journal-title":"Cell Stem Cell"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1242\/dev.146928","article-title":"ID4 levels dictate the stem cell state in mouse spermatogonia","volume":"144","author":"Helsel","year":"2017","journal-title":"Development"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1016\/j.celrep.2018.10.026","article-title":"The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids","volume":"25","author":"Hermann","year":"2018","journal-title":"Cell Reports"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/j.1365-2443.2008.01171.x","article-title":"GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells","volume":"13","author":"Jijiwa","year":"2008","journal-title":"Genes to Cells"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.103861","article-title":"Enrichment of mouse spermatogonial stem cells by melanoma cell adhesion molecule expression","volume":"87","author":"Kanatsu-Shinohara","year":"2012","journal-title":"Biology of Reproduction"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09982-5","article-title":"CUT&Tag for efficient epigenomic profiling of small samples and single cells","volume":"10","author":"Kaya-Okur","year":"2019","journal-title":"Nature Communications"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"3264","DOI":"10.1038\/s41596-020-0373-x","article-title":"Efficient low-cost chromatin profiling with CUT&Tag","volume":"15","author":"Kaya-Okur","year":"2020","journal-title":"Nature Protocols"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/ng0897-358","article-title":"Bcl-2 and Bax function independently to regulate cell death","volume":"16","author":"Knudson","year":"1997","journal-title":"Nature Genetics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1101\/gr.192237.115","article-title":"Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells","volume":"25","author":"Kowalczyk","year":"2015","journal-title":"Genome Research"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1095\/biolreprod.104.029207","article-title":"Culture conditions and single growth factors affect fate determination of mouse spermatogonial stem cells","volume":"71","author":"Kubota","year":"2004","journal-title":"Biology of Reproduction"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.1101\/gad.907301","article-title":"The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis","volume":"15","author":"Kume","year":"2001","journal-title":"Genes & Development"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04827-z","article-title":"Identification of dynamic undifferentiated cell states within the male germline","volume":"9","author":"La","year":"2018","journal-title":"Nature Communications"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.1007\/s00018-019-03201-6","article-title":"Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion","volume":"76","author":"La","year":"2019","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1093\/nsr\/nwy163","article-title":"DAZL is a master translational regulator of murine spermatogenesis","volume":"6","author":"Li","year":"2019","journal-title":"National Science Review"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1242\/dev.105130","article-title":"DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells","volume":"141","author":"Liao","year":"2014","journal-title":"Development"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1006\/geno.1997.4695","article-title":"Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures","volume":"41","author":"Miura","year":"1997","journal-title":"Genomics"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1159\/000445027","article-title":"Characterization of kidney and skeleton phenotypes of mice double heterozygous for Foxc1 and Foxc2","volume":"201","author":"Motojima","year":"2016","journal-title":"Cells Tissues Organs"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.devcel.2007.01.002","article-title":"Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis","volume":"12","author":"Nakagawa","year":"2007","journal-title":"Developmental Cell"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1126\/science.1182868","article-title":"Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment","volume":"328","author":"Nakagawa","year":"2010","journal-title":"Science"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109875","article-title":"A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis","volume":"37","author":"Nakagawa","year":"2021","journal-title":"Cell Reports"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nrc2608","article-title":"DNA topoisomerase II and its growing repertoire of biological functions","volume":"9","author":"Nitiss","year":"2009","journal-title":"Nature Reviews. Cancer"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"25842","DOI":"10.1074\/jbc.M703474200","article-title":"Glial cell line-derived neurotrophic factor regulation of genes essential for self-renewal of mouse spermatogonial stem cells is dependent on Src family kinase signaling","volume":"282","author":"Oatley","year":"2007","journal-title":"The Journal of Biological Chemistry"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nmeth.4150","article-title":"Single-cell mRNA quantification and differential analysis with Census","volume":"14","author":"Qiu","year":"2017","journal-title":"Nature Methods"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nature Methods"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/sj.emboj.7601668","article-title":"TAO kinases mediate activation of p38 in response to DNA damage","volume":"26","author":"Raman","year":"2007","journal-title":"The EMBO Journal"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"2845","DOI":"10.1242\/dev.069088","article-title":"Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage","volume":"139","author":"Relaix","year":"2012","journal-title":"Development"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nature13255","article-title":"mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert)","volume":"510","author":"Rodgers","year":"2014","journal-title":"Nature"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1096\/fj.06-7035com","article-title":"Absence of tektin 4 causes asthenozoospermia and subfertility in male mice","volume":"21","author":"Roy","year":"2007","journal-title":"FASEB Journal"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1172\/JCI80454","article-title":"FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature","volume":"125","author":"Sabine","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1126\/science.1172645","article-title":"The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells","volume":"325","author":"Sada","year":"2009","journal-title":"Science"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1002\/dvg.22036","article-title":"Generation of conditional alleles for Foxc1 and Foxc2 in mice","volume":"50","author":"Sasman","year":"2012","journal-title":"Genesis"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43352","article-title":"Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF","volume":"8","author":"Sharma","year":"2019","journal-title":"eLife"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/humupd\/dmz006","article-title":"Spermatogonial stem cells: updates from specification to clinical relevance","volume":"25","author":"Sharma","year":"2019","journal-title":"Human Reproduction Update"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108752","article-title":"An mTORC1-dependent switch orchestrates the transition between mouse spermatogonial stem cells and clones of progenitor spermatogonia","volume":"34","author":"Suzuki","year":"2021","journal-title":"Cell Reports"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.stem.2019.01.010","article-title":"Human spermatogonial stem cells scrutinized under the single-cell magnifying glass","volume":"24","author":"Tan","year":"2019","journal-title":"Cell Stem Cell"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0027-5107(93)90159-d","article-title":"A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H\/101 F1 hybrid mouse","volume":"290","author":"Tegelenbosch","year":"1993","journal-title":"Mutation Research"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1095\/biolreprod.106.053181","article-title":"CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes","volume":"76","author":"Tokuda","year":"2007","journal-title":"Biology of Reproduction"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.stemcr.2017.01.006","article-title":"SHISA6 Confers Resistance to Differentiation-Promoting Wnt\/\u03b2-Catenin Signaling in Mouse Spermatogenic Stem Cells","volume":"8","author":"Tokue","year":"2017","journal-title":"Stem Cell Reports"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/s0925-4773(00)00283-5","article-title":"Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development","volume":"93","author":"Toyooka","year":"2000","journal-title":"Mechanisms of Development"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nature Biotechnology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.dnarep.2004.08.008","article-title":"Mismatch repair protein Msh2 contributes to UVB-induced cell cycle arrest in epidermal and cultured mouse keratinocytes","volume":"4","author":"van Oosten","year":"2005","journal-title":"DNA Repair"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.stem.2019.01.001","article-title":"Stem cell quiescence: Dynamism, restraint, and cellular idling","volume":"24","author":"van Velthoven","year":"2019","journal-title":"Cell Stem Cell"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nature13851","article-title":"Identification of multipotent mammary stem cells by protein C receptor expression","volume":"517","author":"Wang","year":"2015","journal-title":"Nature"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.stem.2018.08.007","article-title":"Single-Cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Stem Cell"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.devcel.2021.01.015","article-title":"N6-methyladenosine modification of MALAT1 promotes metastasis via reshaping nuclear speckles","volume":"56","author":"Wang","year":"2021","journal-title":"Developmental Cell"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1083\/jcb.200303167","article-title":"Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss","volume":"162","author":"Weaver","year":"2003","journal-title":"The Journal of Cell Biology"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1089\/scd.2017.0233","article-title":"The forkhead transcription factor FOXC2 is required for maintaining murine spermatogonial stem cells","volume":"27","author":"Wei","year":"2018","journal-title":"Stem Cells and Development"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"21045","DOI":"10.1074\/jbc.M112.355321","article-title":"RNA Processing and Modification Protein, Carbon Catabolite Repression 4 (Ccr4), Arrests the Cell Cycle through p21-dependent and p53-independent Pathway","volume":"287","author":"Yi","year":"2012","journal-title":"Journal of Biological Chemistry"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/s1097-2765(00)80404-9","article-title":"The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility","volume":"5","author":"Yuan","year":"2000","journal-title":"Molecular Cell"},{"key":"bib74","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-9-38","article-title":"The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse","volume":"9","author":"Zheng","year":"2009","journal-title":"BMC Developmental Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/85380\/elife-85380-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/85380\/elife-85380-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/85380","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T19:05:05Z","timestamp":1697223905000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/85380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,23]]},"references-count":74,"alternative-id":["10.7554\/eLife.85380"],"URL":"https:\/\/doi.org\/10.7554\/elife.85380","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.7554\/eLife.85380.2","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.12.20.521179","asserted-by":"subject"}],"references":[{"id-type":"accession","id":"GSE112013","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.85380.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.85380.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.85380.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE183163","asserted-by":"subject"},{"id-type":"accession","id":"GSE180729","asserted-by":"subject"},{"id-type":"accession","id":"GSE180926","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,23]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP85380"}}