Promiscuous gene expression (pGE) of numerous self-antigens in thymic epithelial cells (TEC) enables the elimination of self-reactive T cells. The autoimmune regulator (Aire) is the only known molecular determinant driving pGE in the thymus but the existence of Aire-independent mechanisms has been inferred. Here, we analyzed the poly(A)+ transcriptome of TEC populations by RNA-sequencing (RNA-seq) in order to reveal differential features of Aire-induced vs. independent pGE. We report an unanticipated effect of Aire deletion on the proliferation and differentiation of cortical TEC. Moreover, the RNA-seq data reveal the breath of Aire-induced and independent pGE in medullary TEC (mTEC) subsets and the extent of thymic peripheral tissue representation. The results suggest that Aire-induced promiscuously expressed transcripts affect several functions with far reaching biological consequences in mTEC. High-throughput characterization of TEC transcriptomes will enable progress in understanding TEC biology and the establishment of self-tolerance. SOURCE: Charles St-Pierre (charles.stpierre78@gmail.com) - Immunobiology - Claude Perreault Montreal University

Pluto Bioinformatics

GSE65617: Differential features of Aire-induced and Aire-independent promiscuous gene expression in thymic epithelial cells