{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:30:51Z","timestamp":1787567451963,"version":"build-2736575974"},"reference-count":38,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC2506100"],"award-info":[{"award-number":["2023YFC2506100"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82303201"],"award-info":[{"award-number":["82303201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82303201"],"award-info":[{"award-number":["82303201"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2017YFA0103800"],"award-info":[{"award-number":["2017YFA0103800"]}]},{"DOI":"10.13039\/501100018609","name":"High-level Hospital Construction Project of Guangdong Provincial People's Hospital","doi-asserted-by":"crossref","award":["DFJHBF202102"],"award-info":[{"award-number":["DFJHBF202102"]}],"id":[{"id":"10.13039\/501100018609","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DFJHBF202102"],"award-info":[{"award-number":["DFJHBF202102"]}],"id":[{"id":"https:\/\/ror.org\/045kpgw45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,23]]},"abstract":"<jats:p>\n                    Declining rates of male fertility pose a significant clinical challenge, while the mechanisms underlying testicular interstitial function remain incompletely understood. Here, we conducted a comprehensive analysis of the single-cell transcriptomic landscape of the murine testicular interstitium across the postnatal lifespan. The investigation unveiled a previously unrecognized population of Cd34\n                    <jats:sup>+<\/jats:sup>\n                    \/Sox4\n                    <jats:sup>+<\/jats:sup>\n                    mesenchymal cells nestled within the interstitium, hinting at their potential as Leydig cell (LC) progenitors. With the aging process of Cd34\n                    <jats:sup>+<\/jats:sup>\n                    \/Sox4\n                    <jats:sup>+<\/jats:sup>\n                    mesenchymal cells, we observed a decline in glutathione levels within the testicular interstitium. Remarkably, these Cd34\n                    <jats:sup>+<\/jats:sup>\n                    \/Sox4\n                    <jats:sup>+<\/jats:sup>\n                    mesenchymal cells exhibited clonogenic self-renewal capacity and a robust propensity to differentiate into LCs. Intriguingly, when transplanted into LC-disrupted or failure models, Cd34\n                    <jats:sup>+<\/jats:sup>\n                    \/Sox4\n                    <jats:sup>+<\/jats:sup>\n                    cells efficiently colonized the testicular interstitium, resulting in a notable increase in testosterone production. Exploring the epigenetic landscape, we identified critical transcription factors, most notably Sox4, governing the stem cell fate of Cd34\n                    <jats:sup>+<\/jats:sup>\n                    \/Sox4\n                    <jats:sup>+<\/jats:sup>\n                    mesenchymal cells. Overall, this comprehensive lifespan-resolved single-cell atlas of testicular interstitial cells provides fundamental insights into LC progenitor biology and regenerative capacity during aging.\n                  <\/jats:p>","DOI":"10.7554\/elife.100396","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T16:50:08Z","timestamp":1766508608000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.100396","source":"Crossref","is-referenced-by-count":1,"title":["A single-cell atlas of the testicular interstitium defines Leydig progenitor networks sustaining Leydig cell homeostasis across the lifespan"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1477-1644","authenticated-orcid":true,"given":"Xiaojia","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Sports Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/01vjw4z39","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kai","family":"Xia","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Meiling","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01vjw4z39","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/03wnxd135","id-type":"ROR","asserted-by":"publisher"}],"name":"Central Laboratory, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Mengzhi","family":"Hong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Meihua","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Weiqiang","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Zhenmin","family":"Lei","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ckdn478","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of OB\/GYN and Women\u2019s Health, University of Louisville School of Medicine","place":["Louisville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3409-5012","authenticated-orcid":true,"given":"Andy Peng","family":"Xiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0774-2571","authenticated-orcid":true,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179585","type":"journal-article","article-title":"Behavior and functional roles of CD34+ mesenchymal cells in mammalian testes","volume":"23","author":"Abe","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1095\/biolreprod65.3.660","type":"journal-article","article-title":"Differentiation of the adult leydig cell population in the postnatal testis1","volume":"65","author":"Chamindrani Mendis-Handagama","year":"2001","journal-title":"Biology of Reproduction"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mce.2009.01.023","type":"journal-article","article-title":"Leydig cells: From stem cells to aging","volume":"306","author":"Chen","year":"2009","journal-title":"Molecular and Cellular Endocrinology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1093\/molehr\/gat076","type":"journal-article","article-title":"Mesenchymal origin of multipotent human testis-derived stem cells in human testicular cell cultures","volume":"20","author":"Chikhovskaya","year":"2014","journal-title":"MHR"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ydbio.2011.01.011","type":"journal-article","article-title":"Two distinct origins for Leydig cell progenitors in the fetal testis","volume":"352","author":"DeFalco","year":"2011","journal-title":"Developmental Biology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1159\/000179780","type":"journal-article","article-title":"Role of androgens in fetal and pubertal development","volume":"18","author":"Forest","year":"1983","journal-title":"Hormone Research"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/978-0-387-09597-4_14","type":"book-chapter","article-title":"The role of the leydig cell in spermatogenic function","volume-title":"Molecular Mechanisms in Spermatogenesis","author":"Ge","year":"2008"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0074-7696(04)33005-6","type":"journal-article","article-title":"Cell biology of leydig cells in the testis","volume":"233","author":"Haider","year":"2004","journal-title":"In International Review of Cytology"},{"key":"bib9","first-page":"62","type":"journal-article","article-title":"Effect of visfatin on testicular steroidogenesis in purified Leydig cells","volume":"24","author":"Hameed","year":"2012","journal-title":"Journal of Ayub Medical College, Abbottabad"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","type":"journal-article","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.aanat.2017.01.009","type":"journal-article","article-title":"Localization pattern of visfatin (NAMPT) in d-galactose induced aged rat testis","volume":"211","author":"Jeremy","year":"2017","journal-title":"Annals of Anatomy = Anatomischer Anzeiger"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1038\/cr.2014.149","type":"journal-article","article-title":"Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction","volume":"24","author":"Jiang","year":"2014","journal-title":"Cell Research"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","type":"journal-article","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nature Communications"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.stem.2015.02.019","type":"journal-article","article-title":"Mesenchymal cell contributions to the stem cell niche","volume":"16","author":"Kfoury","year":"2015","journal-title":"Cell Stem Cell"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"743","DOI":"10.14670\/HH-19.743","type":"journal-article","article-title":"Distribution and role of CD34-positive stromal cells and myofibroblasts in human normal testicular stroma","volume":"19","author":"Kuroda","year":"2004","journal-title":"Histology and Histopathology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1210\/endo-119-4-1641","type":"journal-article","article-title":"Characterization of insulin and insulin-like growth factor I receptors of purified Leydig cells and their role in steroidogenesis in primary culture: a comparative study","volume":"119","author":"Lin","year":"1986","journal-title":"Endocrinology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1242\/dev.135756","type":"journal-article","article-title":"Mapping lineage progression of somatic progenitor cells in the mouse fetal testis","volume":"143","author":"Liu","year":"2016","journal-title":"Development"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.mce.2008.07.016","type":"journal-article","article-title":"Leydig cell aging and the mechanisms of reduced testosterone synthesis","volume":"299","author":"Midzak","year":"2009","journal-title":"Molecular and Cellular Endocrinology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1530\/REP-08-0377","type":"journal-article","article-title":"NAMPT (visfatin) in the chicken testis: influence of sexual maturation on cellular localization, plasma levels and gene and protein expression","volume":"139","author":"Oc\u00f3n-Grove","year":"2010","journal-title":"REPRODUCTION"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"R151","DOI":"10.1530\/REP-16-0588","type":"journal-article","article-title":"Role of the testis interstitial compartment in spermatogonial stem cell function","volume":"153","author":"Potter","year":"2017","journal-title":"Reproduction"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nmeth.4150","type":"journal-article","article-title":"Single-cell mRNA quantification and differential analysis with Census","volume":"14","author":"Qiu","year":"2017","journal-title":"Nature Methods"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1016\/0303-7207(90)90242-z","type":"journal-article","article-title":"Mesenchymal-epithelial cell interactions in the ovary: estrogen-induced theca cell steroidogenesis","volume":"72","author":"Roberts","year":"1990","journal-title":"Molecular and Cellular Endocrinology"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24130-8","type":"journal-article","article-title":"TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice","volume":"12","author":"Shen","year":"2021","journal-title":"Nature Communications"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1210\/me.2015-1200","type":"journal-article","article-title":"Fetal leydig cells persist as an androgen-independent subpopulation in the postnatal testis","volume":"29","author":"Shima","year":"2015","journal-title":"Molecular Endocrinology"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1242\/dev.169136","type":"journal-article","article-title":"Fetal Leydig cells dedifferentiate and serve as adult Leydig stem cells","volume":"145","author":"Shima","year":"2018","journal-title":"Development"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","type":"journal-article","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.cell.2020.11.041","type":"journal-article","article-title":"Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma","volume":"184","author":"Sun","year":"2021","journal-title":"Cell"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","type":"journal-article","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":"bib29","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.semcdb.2016.03.003","type":"journal-article","article-title":"Development, function and fate of fetal Leydig cells","volume":"59","author":"Wen","year":"2016","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.cell.2013.03.035","type":"journal-article","article-title":"Master transcription factors and mediator establish super-enhancers at key cell identity genes","volume":"153","author":"Whyte","year":"2013","journal-title":"Cell"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","type":"journal-article","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","type":"journal-article","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1002\/stem.2569","type":"journal-article","article-title":"Transplantation of CD51+ stem leydig cells: a new strategy for the treatment of testosterone deficiency","volume":"35","author":"Zang","year":"2017","journal-title":"Stem Cells"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jare.2022.12.007","type":"journal-article","article-title":"A single-cell transcriptomic landscape of mouse testicular aging","volume":"53","author":"Zhang","year":"2023","journal-title":"Journal of Advanced Research"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1093\/biolre\/ioy059","type":"journal-article","article-title":"Leydig cells: formation, function, and regulation","volume":"99","author":"Zirkin","year":"2018","journal-title":"Biology of Reproduction"},{"key":"dataset1","type":"dataset","article-title":"A comprehensive atlas of testicular interstitium reveals Cd34+\/Sox4+ mesenchymal cells as potential Leydig cell progenitors","volume-title":"NCBI Gene Expression Omnibus","author":"Huang","year":"2024","unstructured":"Huang X, Xia K, Yang M, Hong M, Jiang M, Li W, Lei Z, Xiang AP, Zhao W. 2024. A comprehensive atlas of testicular interstitium reveals Cd34+\/Sox4+ mesenchymal cells as potential Leydig cell progenitors. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE262415. GSE262415."},{"key":"dataset2","type":"dataset","article-title":"A comprehensive atlas of testicular interstitium reveals Cd34+\/Sox4+ mesenchymal cells as potential Leydig cell progenitors","volume-title":"NCBI Gene Expression Omnibus","author":"Huang","year":"2024","unstructured":"Huang X, Xia K, Yang M, Hong M, Jiang M, Li W, Lei Z, Xiang AP, Zhao W. 2024. A comprehensive atlas of testicular interstitium reveals Cd34+\/Sox4+ mesenchymal cells as potential Leydig cell progenitors. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE262416. GSE262416."},{"key":"dataset3","type":"dataset","article-title":"Neonatal and adult human testis defined at the single-cell level","volume-title":"NCBI Gene Expression Omnibus","author":"Sohni","year":"2018","unstructured":"Sohni A, Tan K, Song HW, Burow D. 2018. Neonatal and adult human testis defined at the single-cell level. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE124263. GSE124263."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/100396\/elife-100396-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/100396\/elife-100396-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/100396","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:15:17Z","timestamp":1787562917000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/100396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,23]]},"references-count":38,"alternative-id":["10.7554\/eLife.100396"],"URL":"https:\/\/doi.org\/10.7554\/elife.100396","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.02.606288","asserted-by":"subject"}],"references":[{"id-type":"accession","id":"GSE124263","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE262415","asserted-by":"subject"},{"id-type":"accession","id":"GSE262416","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.100396.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.100396.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.100396.sa0","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,23]]},"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":"e100396"}}