{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:48:34Z","timestamp":1781164114465,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JM\u2010065"],"award-info":[{"award-number":["2020JM\u2010065"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JQ\u2010098"],"award-info":[{"award-number":["2020JQ\u2010098"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2021JQ\u2010025"],"award-info":[{"award-number":["2021JQ\u2010025"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771673"],"award-info":[{"award-number":["81771673"]}],"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":["81820108017"],"award-info":[{"award-number":["81820108017"]}],"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":["82101826"],"award-info":[{"award-number":["82101826"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M653673"],"award-info":[{"award-number":["2019M653673"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Early T\u2010cell development from CD4<jats:sup>\u2212<\/jats:sup>\u00a0CD8<jats:sup>\u2212<\/jats:sup> double\u2010negative (DN) stage to CD4<jats:sup>+<\/jats:sup>\u00a0CD8<jats:sup>+<\/jats:sup> double\u2010positive (DP) stage in the thymus is regulated through multiple steps involving a batch of sequentially expressed factors. Our preliminary data and a recent report showed that AT\u2010rich interaction domain 1A (Arid1a) is required for the transition from DN to DP stages, but the mechanism is not fully understood. In this study, we consolidated that conditional deletion of Arid1a in T\u2010cell lineage intrinsically caused developmental blocks from DN3 to DN4\u00a0stages, as well as from DN4 to DP stages using both in vivo adoptive T\u2010cell transfer model and in vitro culture system. The expression of intracellular TCR\u03b2 is significantly decreased in Arid1a\u2010deficient DN4 cells compared with WT cells. OT1 transgenic TCR can rescue the defect in the transition from DN3 to DN4\u00a0stages, but not from DN to DP stages. Furthermore, we observed a comparable or stronger proliferation capacity accompanied by a significant increase in cell death in Arid1a<jats:sup>\u2212\/\u2212<\/jats:sup> DP cells compared with that in WT controls. RNA\u2010Seq analysis shows a significant enrichment of apoptotic pathway within differentially expressed genes between Arid1a<jats:sup>\u2212\/\u2212<\/jats:sup> and WT DP cells, including the upregulation of <jats:italic>Bim<\/jats:italic>, <jats:italic>Casp3<\/jats:italic> and <jats:italic>Trp53<\/jats:italic> and the downregulation of <jats:italic>Rorc<\/jats:italic>, <jats:italic>Bcl<\/jats:italic>\u2010<jats:italic>XL<\/jats:italic> and <jats:italic>Mcl1<\/jats:italic>. Therefore, our study reveals a novel mechanism that Arid1a controls early T\u2010cell development by maintaining intracellular TCR\u03b2 expression\u2010mediated \u03b2\u2010selection and activating parallel cell survival pathways.<\/jats:p>","DOI":"10.1111\/imm.13440","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T15:18:21Z","timestamp":1639840701000},"page":"402-413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Arid1a promotes thymocyte development through \u03b2\u2010selection\u2010dependent and \u03b2\u2010selection\u2010independent mechanisms"],"prefix":"10.1111","volume":"165","author":[{"given":"Xiaofeng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University) Ministry of Education  Xi'an China"},{"name":"Xi'an Key Laboratory of Immune Related Diseases  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University) Ministry of Education  Xi'an China"},{"name":"Xi'an Key Laboratory of Immune Related Diseases  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Zou","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjun","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cangang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"Xi'an Key Laboratory of Immune Related Diseases  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-4304","authenticated-orcid":false,"given":"Baojun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology School of Basic Medical Sciences; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of Infection and Immunity Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University) Ministry of Education  Xi'an China"},{"name":"Xi'an Key Laboratory of Immune Related Diseases  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.10.4244"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:34:2:117"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636503"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.7.4235"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2507"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-5323(02)00064-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80084-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807557106"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902846"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91127"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.073"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290345"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00654-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08911"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3068"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00127-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.23.6979"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00199-7"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030714"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1481"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.7088"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181076198"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402144200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900959"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046590"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.829"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154008"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.07.017"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061020"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01549-13"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1475"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00917-10"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1139\/o11-042"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00876"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032092"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801802105"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.076"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13440","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13440","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T03:14:34Z","timestamp":1748920474000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,27]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/imm.13440"],"URL":"https:\/\/doi.org\/10.1111\/imm.13440","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,27]]},"assertion":[{"value":"2021-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}