{"doi":"10.1016/j.devcel.2024.09.011","title":"Sex-biased human thymic architecture guides T cell development through spatially defined niches","abstract":"Within the thymus, regulation of the cellular crosstalk directing T cell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding human postnatal T cell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both T cell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population of extracellular matrix (ECM) − fibroblasts, and characterize the medullary niches surrounding Hassall’s corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females. • Spatial multiomics show sex differences in early postnatal T cell development • JAG1 skews early thymic progenitor development toward thymic dendritic cells • Thymocytes may self-select to support positive selection of αβT cells • Hassall’s corpuscles organize negative selection niches in the medulla Stankiewicz et al. generate a spatial multiomic resource of human postnatal thymus. Using a niche-centric approach, they show that sex-based differences in thymus biology and T cell development arise before puberty, providing an essential contribution to our understanding of the mechanisms underlying immune function and dysfunction in males and females.","journal":"Developmental Cell","year":2024,"id":424812,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9038,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1167039,"name":"Kevin Salim","orcid":"0000-0003-3793-0415","position":1,"is_corresponding":false},{"id":1167315,"name":"Emily A Flaschner","orcid":null,"position":2,"is_corresponding":false},{"id":243026,"name":"Yu Xin Wang","orcid":"0000-0001-8440-9388","position":3,"is_corresponding":false},{"id":1167040,"name":"John M. Edgar","orcid":"0000-0001-5678-6485","position":4,"is_corresponding":false},{"id":1221818,"name":"Lauren J. Durland","orcid":"0000-0001-5740-8670","position":5,"is_corresponding":false},{"id":1167316,"name":"Bruce Z B Lin","orcid":null,"position":6,"is_corresponding":false},{"id":994515,"name":"Grace C. Bingham","orcid":"0000-0002-5223-0460","position":7,"is_corresponding":false},{"id":1167317,"name":"Matthew C. Major","orcid":null,"position":8,"is_corresponding":false},{"id":267923,"name":"Ross D. Jones","orcid":"0000-0003-0891-6761","position":9,"is_corresponding":false},{"id":243030,"name":"Helen M. Blau","orcid":"0000-0001-6503-5480","position":10,"is_corresponding":false},{"id":258275,"name":"Elizabeth J. Rideout","orcid":"0000-0003-0012-2828","position":11,"is_corresponding":false},{"id":685436,"name":"Megan K. Levings","orcid":"0000-0002-0305-5790","position":12,"is_corresponding":false},{"id":1167041,"name":"Peter W. Zandstra","orcid":"0000-0002-9568-733X","position":13,"is_corresponding":false},{"id":629929,"name":"Fábio Rossi","orcid":"0000-0002-0368-2620","position":14,"is_corresponding":false},{"id":1167038,"name":"Laura N Stankiewicz","orcid":"0000-0002-3982-5558","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-19T01:58:21.523756Z","pmid":"39383865","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":[]}