{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:42Z","timestamp":1789625022684,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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                    Early thymic progenitors (ETPs) retain the potential for alternative fates but commit to the T-cell lineage as they progress through the CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double-negative (DN) thymocyte stages early in T-cell development. Current evidence suggests that T-lineage commitment occurs during the transition from the DN2a to DN2b stage, a process characterized by downregulation of c-KIT and CD44 expression. Moreover, Bcl11b activation in DN2a thymocytes closely coincides with T-lineage commitment. Despite this heterogeneity in Bcl11b-YFP expression within DN2a thymocytes, these cells have predominantly been studied as a single population due to the absence of cell-surface markers capable of resolving the corresponding substages. To define the T-lineage commitment transition process at higher resolution, we profiled c-KIT-expressing DN thymocytes in the mouse thymus using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). This revealed heterogeneity within DN2a thymocytes. We identified two subpopulations, which we termed DN2a-1 and DN2a-2, based on differences in CD34, CD90, and\n                    <jats:italic>Bcl11b<\/jats:italic>\n                    expression. DN2a-1 thymocytes co-expressed multipotency and T-lineage-associated markers, whereas DN2a-2 cells mainly displayed a transcriptional profile consistent with T-lineage commitment. Functional assays demonstrated that DN2a-1 thymocytes were more developmentally advanced than ETPs but remained multipotent, whereas DN2a-2 thymocytes were more mature and largely restricted to the T lineage. Furthermore,\n                    <jats:italic>in vivo<\/jats:italic>\n                    clonal lineage tracing indicated that these subsets were on a developmental continuum. Together, these findings reveal that the heterogeneous DN2a stage can be resolved further by CD90 expression into pre- and post-T lineage-restricted subsets.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1940310","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:52Z","timestamp":1789623112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Upregulation of CD90 correlates with T lineage commitment at the DN2a stage of T cell development"],"prefix":"10.3389","volume":"17","author":[{"given":"Dhruti","family":"Parikh","sequence":"first","affiliation":[{"name":"St Vincent\u2019s Institute of Medical Research","place":["Fitzroy, VIC, Australia"]},{"name":"Department of Medicine (St Vincent\u2019s), University of Melbourne","place":["Fitzroy, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gu","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute of Medical Research","place":["Fitzroy, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tomei","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research","place":["Parkville, VIC, Australia"]},{"name":"Department of Medical Biology, University of Melbourne","place":["Parkville, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom S.","family":"Weber","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research","place":["Parkville, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalin H.","family":"Naik","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research","place":["Parkville, VIC, Australia"]},{"name":"Department of Medical Biology, University of Melbourne","place":["Parkville, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M. 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