{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:00:25Z","timestamp":1790373625902,"version":"4.1.0"},"reference-count":91,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1000702"],"award-info":[{"award-number":["2021YFF1000702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402755"],"award-info":[{"award-number":["32402755"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32441081"],"award-info":[{"award-number":["32441081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YDZX2025004"],"award-info":[{"award-number":["YDZX2025004"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Reproduction is a fundamental biological process regulated by complex cellular and molecular networks across the neuroendocrine and reproductive systems. To explore conserved and species\u2010specific mechanisms of fertility regulation, we constructed a high\u2010resolution single\u2010cell transcriptomic atlas of\u00a015 reproductive and central nervous system (CNS) tissues from sheep and integrated it with human single\u2010cell datasets from 13 matched tissues. This comparative atlas comprises over 1.09 million cells and identifies\u00a076 major cell types across species. Cross\u2010species integration based on 15\u00a0748 orthologous genes revealed that 54 cell types (71.1%) are shared between sheep and humans, showing strong conservation in transcriptional programs, cell lineage trajectories, and regulatory networks. Integrating genome\u2010wide association studies (GWAS) for sheep lifetime average litter size with the single\u2010cell atlas identified crucial\u00a0fertility\u2010associated genes and signaling pathways. Cell\u2013cell communication analysis revealed UNC5\u2013SLIT\u2013BMP signaling cascades coordinating neuroendocrine regulation of fertility along the hypothalamus\u2013pituitary\u2013ovary (HPO) axis. Trait\u2013cell type enrichment analyses for 41 human complex traits further demonstrated that conserved reproductive and CNS cell types in sheep recapitulate key human GWAS associations. Together, this cross\u2010species single\u2010cell atlas (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/csca.njau.edu.cn\/\">https:\/\/csca.njau.edu.cn\/<\/jats:ext-link>\n                    ) provides a valuable resource for understanding how conserved cellular programs and inter\u2010organ signaling networks regulate fertility and other complex traits.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517633","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:10:48Z","timestamp":1769058648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Single\u2010Cell Transcriptomic Atlas Reveals the Genetic Regulation of Reproductive Traits"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0140-8654","authenticated-orcid":false,"given":"Bingru","family":"Zhao","sequence":"first","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6211-3834","authenticated-orcid":false,"given":"Hanpeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dailu","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Animal Science University of California\u2010Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetics Breeding and Reproduction of Xinjiang Wool\u2010Sheep Cashmere\u2010goat (XJYS1105) Institute of Animal Science Xinjiang Academy of Animal Sciences  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglai","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-7774","authenticated-orcid":false,"given":"Yanli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Livestock Embryo Engineering Laboratory College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/gpbjnl\/qzaf020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.277372.12"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252806"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010024\u201003288\u20106"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016485\u20101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2019.106175"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12309"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201097865\u20109"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.05.011"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091577598"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msae058"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009\u20100461"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201313"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dml056"},{"key":"e_1_2_10_16_1","first-page":"1","article-title":"Sheep as a Model for Neuroendocrinology Research","volume":"189","author":"Foradori C. D.","year":"2022","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11091251"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112422"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103476(75)80128\u20104"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1110551"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2013.02.012"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copsyc.2018.07.011"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007813"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010023\u201001412\u2010z"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011881\u20108"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010019\u20100290\u20100"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001857\u2010w"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010025\u201002156\u20108"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27041"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.70038"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-018-0590-4","article-title":"Logistical c, Organ c, Processing, Library p, Sequencing, Computational Data a, Cell Type a, Writing G, Et al. Single\u2010Cell Transcriptomics of 20 Mouse Organs Creates a Tabula Muris","volume":"562","author":"C T. M.","year":"2018","journal-title":"Nature"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010019\u20101862\u20105"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010021\u201000332\u20102"},{"key":"e_1_2_10_34_1","first-page":"205","article-title":"A Benchmark of Gene Expression Tissue\u2010Specificity Metrics","volume":"18","author":"Kryuchkova\u2010Mostacci N.","year":"2017","journal-title":"Briefings in Bioinformatics"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010025\u201002329\u20105"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305175"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101198R"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.019"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12637"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010019\u20101663\u2010x"},{"key":"e_1_2_10_42_1","article-title":"Mapping single\u2010cell developmental potential in health and disease with interpretable deep learning","author":"Kang M.","year":"2024","journal-title":"bioRxiv"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.026"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2728"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.045"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010018\u20100995\u2010y"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002097"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100383"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010024\u201001045\u20104"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000847\u20106"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19102973"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/diseases12050090"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000072"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102496\u20101"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4896"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41559\u2010023\u201002186\u20107"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101506\u20107"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131199"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmh011"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010025\u201008277\u20104"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011036\u20109"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090400"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010025\u201011621\u2010x"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914812"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8502"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40104\u2010023\u201000941\u20101"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12172169"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001767\u2010y"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010020\u20101950\u20106"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100619\u20100"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028803\u2010w"},{"key":"e_1_2_10_75_1","article-title":"clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu T.","year":"2021","journal-title":"Innovation"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.024"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201055146\u20105"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4237"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003282\u20100"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3715005"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh103"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv098"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010020\u201000756\u20100"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2310"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/rssb.12388"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32894"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202517633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202517633","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202517633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:21:47Z","timestamp":1790371307000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202517633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":91,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/advs.202517633"],"URL":"https:\/\/doi.org\/10.1002\/advs.202517633","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e17633"}}