{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:33:41Z","timestamp":1790670821276,"version":"4.1.0"},"reference-count":63,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["3217080356"],"award-info":[{"award-number":["3217080356"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771673"],"award-info":[{"award-number":["81771673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010904","name":"Major International Joint Research Programme","doi-asserted-by":"crossref","award":["81820108017"],"award-info":[{"award-number":["81820108017"]}],"id":[{"id":"10.13039\/501100010904","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,2,3]]},"abstract":"<jats:p>\n                    T-cell development in the thymus undergoes the process of differentiation, selective proliferation, and survival from CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double negative (DN) stage to CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    double positive (DP) stage prior to the formation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    helper and CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytolytic T cells ready for circulation. Each developmental stage is tightly regulated by sequentially operating molecular networks, of which only limited numbers of transcription regulators have been deciphered. Here, we identified Zfp335 transcription factor as a new player in the regulatory network controlling thymocyte development in mice. We demonstrate that\n                    <jats:italic>Zfp335<\/jats:italic>\n                    intrinsically controls DN to DP transition, as T-cell-specific deficiency in\n                    <jats:italic>Zfp335<\/jats:italic>\n                    leads to a substantial accumulation of DN3 along with reduction of DP, CD4\n                    <jats:sup>+<\/jats:sup>\n                    , and CD8\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes. This developmental blockade at DN stage results from the impaired intracellular TCR\u03b2 (iTCR\u03b2) expression as well as increased susceptibility to apoptosis in thymocytes. Transcriptomic and ChIP-seq analyses revealed a direct regulation of transcription factors\n                    <jats:italic>Bcl6<\/jats:italic>\n                    and\n                    <jats:italic>Rorc<\/jats:italic>\n                    by Zfp335. Importantly, enhanced expression of TCR\u03b2 and\n                    <jats:italic>Bcl6\/Rorc<\/jats:italic>\n                    restores the developmental defect during DN3 to DN4 transition and improves thymocytes survival, respectively. These findings identify a critical role of\n                    <jats:italic>Zfp335<\/jats:italic>\n                    in controlling T-cell development by maintaining iTCR\u03b2 expression-mediated \u03b2-selection and independently activating cell survival signaling.\n                  <\/jats:p>","DOI":"10.7554\/elife.75508","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T08:00:12Z","timestamp":1643875212000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.75508","source":"Crossref","is-referenced-by-count":11,"title":["Zinc finger protein Zfp335 controls early T-cell development and survival through \u03b2-selection-dependent and -independent mechanisms"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1624-8241","authenticated-orcid":true,"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zhmm22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University","place":["Xi'an, China"]},{"id":[{"id":"https:\/\/ror.org\/017zhmm22","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjun","family":"Jiao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zhmm22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an 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