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Here, we combine single cell (sc) RNA gene expression and sc \u03b3\u03b4 T cell receptor (TCR) sequencing on fetal and pediatric \u03b3\u03b4 thymocytes in order to understand the ontogeny of human \u03b3\u03b4 T cells. Mature fetal \u03b3\u03b4 thymocytes (both the V\u03b39V\u03b42 and nonV\u03b39V\u03b42 subsets) are committed to either a type 1, a type 3 or a type 2-like effector fate displaying a wave-like pattern depending on gestation age, and are enriched for public CDR3 features upon maturation. Strikingly, these effector modules express different CDR3 sequences and follow distinct developmental trajectories. In contrast, the pediatric thymus generates only a small effector subset that is highly biased towards V\u03b39V\u03b42 TCR usage and shows a mixed type 1\/type 3 effector profile. Thus, our combined dataset of gene expression and detailed TCR information at the single-cell level identifies distinct functional thymic programming of \u03b3\u03b4 T cell immunity in human.<\/jats:p>","DOI":"10.1038\/s41467-022-33488-2","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:02:36Z","timestamp":1664841756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Identification of distinct functional thymic programming of fetal and pediatric human \u03b3\u03b4 thymocytes via single-cell analysis"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-1748","authenticated-orcid":false,"given":"Guillem","family":"Sanchez Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-1993","authenticated-orcid":false,"given":"Maria","family":"Papadopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8626-4370","authenticated-orcid":false,"given":"Abdulkader","family":"Azouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-6244","authenticated-orcid":false,"given":"Yohannes","family":"Tafesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archita","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry K. 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