Abstract
BACKGROUND: Thymic epithelial cells (TECs) play a crucial role in thymoma pathogenesis and associated autoimmune conditions. This study aims to elucidate the alterations in gene expression and cellular composition of TECs within type B thymomas, which are often associated with autoimmune diseases. METHODS: We conducted single-cell RNA sequencing (scRNA-seq) on TECs isolated from both tumor and normal regions in type B thymoma patients. Using droplet-based scRNA-seq, we analyzed 15,062 tumor-derived TECs and 16,541 normal TECs from three patients of type B thymoma. RESULTS: Cell clustering analysis revealed increased cortical TECs (cTECs) and decreased specific subsets of medullary TECs (mTECs) in tumor regions compared to normal regions. Differential gene expression analysis further highlighted distinct transcriptional profiles between TEC subsets from tumor and normal regions. Notably, genes typically expressed in normal cTECs were aberrantly up-regulated in mTEC subsets within the tumor regions. To uncover the underlying mechanisms driving these gene expression changes, we focused on transcription factors differentially expressed in tumor TECs. Based on these insights, we established a mouse model that partially mirrors the gene expression profile observed in thymoma. This model provides a valuable tool for investigating the potential roles of these gene expression changes in thymoma-associated autoimmune diseases. CONCLUSIONS: Our findings underscore the importance of altered TEC subsets and their gene expression profiles in thymoma development and associated autoimmunity, offering new avenues for therapeutic intervention.