{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:52Z","timestamp":1787026612496,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The \u03b1\u03b2 and \u03b3\u03b4 T cell lineages both differentiate in the thymus from common uncommitted progenitors. The earliest stage of T cell development is known as CD4\n                    <jats:sup>-<\/jats:sup>\n                    CD8\n                    <jats:sup>-<\/jats:sup>\n                    double negative 1 (DN1), which has previously been shown to be a heterogenous mixture of cells. Of these, only the CD117\n                    <jats:sup>+<\/jats:sup>\n                    fraction has been proposed to be true T cell progenitors that progress to the DN2 and DN3 thymocyte stages, at which point the development of the \u03b1\u03b2 and \u03b3\u03b4 T cell lineages diverge. However, recently, it has been shown that at least some \u03b3\u03b4 T cells may be derived from a subset of CD117\n                    <jats:sup>-<\/jats:sup>\n                    DN thymocytes. Along with other ambiguities, this suggests that T cell development may not be as straightforward as previously thought. To better understand early T cell development, particularly the heterogeneity of DN1 thymocytes, we performed a single cell RNA sequence (scRNAseq) of mouse DN and \u03b3\u03b4 thymocytes and show that the various DN stages indeed comprise a transcriptionally diverse subpopulations of cells. We also show that multiple subpopulations of DN1 thymocytes exhibit preferential development towards the \u03b3\u03b4 lineage. Furthermore, specific \u03b3\u03b4-primed DN1 subpopulations preferentially develop into IL-17 or IFN\u03b3-producing \u03b3\u03b4 T cells. We show that DN1 subpopulations that only give rise to IL-17-producing \u03b3\u03b4 T cells already express many of the transcription factors associated with type 17 immune cell responses, while the DN1 subpopulations that can give rise to IFN\u03b3-producing \u03b3\u03b4 T cell already express transcription factors associated with type 1 immune cell responses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2023.1106652","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T01:30:40Z","timestamp":1680485440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Distinct subpopulations of DN1 thymocytes exhibit preferential \u03b3\u03b4 T lineage potential"],"prefix":"10.3389","volume":"14","author":[{"given":"Seungyoul","family":"Oh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tomei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod P.","family":"Skinner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart P.","family":"Berzins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalin H.","family":"Naik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H. 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