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Consistent with this, the disruption of mTEC development had functional consequences, including alterations in tuft-associated iNKT polarization and microfold-associated B-cell class switching. In addition, high-resolution transcriptomics revealed that Fezf2 and Aire regulate distinct transcriptional programs, with Fezf2 driving both activation and repression of a more limited set of tissue-restricted genes compared to the broad gene activation program observed for Aire. Pure transcriptional repression at Fezf2 target loci was sufficient to partially rescue mTEC development in global Fezf2-\/- (tKO) mice, potentially through suppression of Lifr expression and modulation of downstream Stat3 signaling tone. These results expand our understanding of Fezf2 in mTEC biology, highlighting transcriptional repression as a required functional facet for adult steady-state lineage patterning across the mTEC compartment.<\/jats:p>","DOI":"10.64898\/2025.12.31.697099","type":"posted-content","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T04:15:10Z","timestamp":1767327310000},"source":"Crossref","is-referenced-by-count":2,"title":["Fezf2 regulates differentiation of Aire-expressing and post-Aire mimetic epithelial populations maintaining thymic homeostasis"],"prefix":"10.64898","author":[{"given":"Joe","family":"Germino","sequence":"first","affiliation":[{"name":"Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Liu","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Medicine, University of California, San Francisco, San 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