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Despite their potential value for immunotherapy, differentiation of \u03b3\u03b4 T cells in the thymus is incompletely understood. Here, we establish a high\u2010resolution map of \u03b3\u03b4 T\u2010cell differentiation from the fetal and adult thymus using single\u2010cell RNA sequencing. We reveal novel sub\u2010types of immature and mature \u03b3\u03b4 T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult \u03b3\u03b4 T\u2010cell differentiation. By performing a combined single\u2010cell analysis of\n                    <jats:italic>Sox13, Maf,<\/jats:italic>\n                    and\n                    <jats:italic>Rorc<\/jats:italic>\n                    knockout mice, we demonstrate sequential activation of these factors during IL\u201017\u2010producing \u03b3\u03b4 T\u2010cell (\u03b3\u03b4T17) differentiation. These findings substantially expand our understanding of \u03b3\u03b4 T\u2010cell ontogeny in fetal and adult life. Our experimental and\u00a0computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages.\n                  <\/jats:p>","DOI":"10.15252\/embj.2019104159","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T16:09:12Z","timestamp":1591632552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Deciphering the regulatory landscape of fetal and adult \u03b3\u03b4 T\u2010cell development at single\u2010cell resolution"],"prefix":"10.1038","volume":"39","author":[{"family":"Sagar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pokrovskii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip S","family":"Herman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Naik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Sock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Zeis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Lausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-3294","authenticated-orcid":false,"given":"Michael","family":"Wegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakup","family":"Tanriver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan R","family":"Littman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-5898","authenticated-orcid":false,"given":"Dominic","family":"Gr\u00fcn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"BFEMBJ2019104159_CR1","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","volume":"11","author":"S Anders","year":"2010","unstructured":"Anders S, Huber W (2010) Differential expression analysis for sequence count data. 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