{"doi":"10.7554/elife.92552","title":"Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium","abstract":"Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here, we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny in mice. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium.","journal":"eLife","year":2023,"id":340433,"datarank":0.5460748619987112,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.1210928603902788,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.1210928603902788,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":11,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9364,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE239913","GSE243180"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314989,"name":"Andrea J. White","orcid":"0000-0001-6950-6729","position":1,"is_corresponding":false},{"id":997723,"name":"Meiting Yang","orcid":null,"position":2,"is_corresponding":false},{"id":695444,"name":"Sayumi Fujimori","orcid":"0000-0002-1822-1296","position":3,"is_corresponding":false},{"id":1074931,"name":"Yu Tanaka","orcid":"0000-0003-3410-6308","position":4,"is_corresponding":false},{"id":696068,"name":"Alison Jacques","orcid":null,"position":5,"is_corresponding":false},{"id":905714,"name":"Hiroshi Kiyonari","orcid":"0000-0002-1509-8747","position":6,"is_corresponding":false},{"id":1074932,"name":"Yosuke Matsushita","orcid":"0000-0003-2528-0291","position":7,"is_corresponding":false},{"id":291035,"name":"Sevilay Turan","orcid":"0000-0003-4205-3162","position":8,"is_corresponding":false},{"id":226280,"name":"Michael C. Kelly","orcid":"0000-0003-0654-2778","position":9,"is_corresponding":false},{"id":314997,"name":"Graham Anderson","orcid":"0000-0002-2917-4085","position":10,"is_corresponding":false},{"id":314995,"name":"Yousuke Takahama","orcid":"0000-0002-4992-9174","position":11,"is_corresponding":false},{"id":314994,"name":"Izumi Ohigashi","orcid":"0000-0003-0017-6957","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:10:54.145367Z","pmid":"38466627","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}