AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma

Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA-seq data in the TCGA-THYM database. Furthermore, our bioinformatics approach to the recent single-cell RNA-seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs.

Automated summary

Despite the physiological distinction between cTECs and mTECs, the origin of TCs and other thymic epithelial tumors has been unclear. By studying the mTEC-specific transcriptional regulator AIRE, it was found that a significant proportion of TCs express AIRE with characteristic nuclear dot morphology. This expression was supported by RNA-seq data and further analysis revealed that TCs exhibit molecular characteristics of multiple mTEC subpopulations, suggesting their derivation from mTECs.