{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:01:07Z","timestamp":1761897667015,"version":"3.41.2"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"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>The underlying mechanisms of thymocyte development and lineage determination remain incompletely understood, and the emerging evidences demonstrated that RNA binding proteins (RBPs) are deeply involved in governing T cell fate in thymus. Serine\/arginine-rich splicing factor 1 (SRSF1), as a classical splicing factor, is a pivotal RBP for gene expression in various biological processes. Our recent study demonstrated that SRSF1 plays essential roles in the development of late thymocytes by modulating the T cell regulatory gene networks post-transcriptionally, which are critical in response to type I interferon signaling for supporting thymocyte maturation. Here, we report SRSF1 also contributes to the determination of the CD8<jats:sup>+<\/jats:sup>T cell fate. By specific ablation of SRSF1 in CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>double positive (DP) thymocytes, we found that SRSF1 deficiency impaired the maturation of late thymocytes and diminished the output of both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>single positive T cells. Interestingly, the ratio of mature CD4<jats:sup>+<\/jats:sup>to CD8<jats:sup>+<\/jats:sup>cells was notably altered and more severe defects were exhibited in CD8<jats:sup>+<\/jats:sup>lineage than those in CD4<jats:sup>+<\/jats:sup>lineage, reflecting the specific function of SRSF1 in CD8<jats:sup>+<\/jats:sup>T cell fate decision. Mechanistically, SRSF1-deficient cells downregulate their expression of<jats:italic>Runx3<\/jats:italic>, which is a crucial transcriptional regulator in sustaining CD8<jats:sup>+<\/jats:sup>single positive (SP) thymocyte development and lineage choice. Moreover, forced expression of Runx3 partially rectified the defects in SRSF1-deficient CD8<jats:sup>+<\/jats:sup>thymocyte maturation. Thus, our data uncovered the previous unknown role of SRSF1 in establishment of CD8<jats:sup>+<\/jats:sup>cell identity.<\/jats:p>","DOI":"10.3389\/fimmu.2022.838719","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T04:41:24Z","timestamp":1643172084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["SRSF1 Deficiency Impairs the Late Thymocyte Maturation and the CD8 Single-Positive Lineage Fate Decision"],"prefix":"10.3389","volume":"13","author":[{"given":"Ce","family":"Ji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunzong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghao","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guotao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanjuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxia","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youmin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3702","article-title":"Developmental Gene Networks: A Triathlon on the Course to T Cell Identity","volume":"14","author":"Yui","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nri2232","article-title":"Launching the T-Cell-Lineage Developmental Programme","volume":"8","author":"Rothenberg","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115715","article-title":"Zoned Out: Functional Mapping of Stromal Signaling Microenvironments in the Thymus","volume":"25","author":"Petrie","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000889","article-title":"Zuniga-Pflucker JC. 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