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Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)\u2010based lineage tracking are profiled in TETs at single\u2010cell resolution. An original subpopulation of KRT14<jats:sup>+<\/jats:sup> progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper\u2010rearrangement state is revealed, due to the lack of CCL21<jats:sup>+<\/jats:sup> medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn\u2010infiltrating mature T cells. These common features based on the single\u2010cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9\u2010SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC\u2010based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1<jats:sup>+<\/jats:sup> CFTR<jats:sup>\u2212<\/jats:sup> ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment.<\/jats:p>","DOI":"10.1002\/advs.202406653","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T08:29:53Z","timestamp":1726043393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Abnormal Cellular Populations Shape Thymic Epithelial Tumor Heterogeneity and Anti\u2010Tumor by Blocking Metabolic Interactions in Organoids"],"prefix":"10.1002","volume":"11","author":[{"given":"Xuefei","family":"Liu","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Institute Zhejiang Cancer Hospital Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou Zhejiang 310022 China"},{"name":"Department of Biochemistry School of Medicine Southern University of Science and Technology  Shenzhen 518055 China"},{"name":"Shenzhen 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