RNA-seq profiling of cortical and medullary thymic epithelial cells from wildtype and Kat7 knockout mice

Thymic epithelial cells (TECs) govern thymic T lymphocyte differentiation and selection. They can be divided into cortical and medullary TECs based on their anatomical location, function and molecular features. Cortical TECs (cTECs) provide the microenvironment for the commitment of haematopoietic precursors to the T lymphoid lineage and mediate the positive selection of CD4+CD8+ double-positive thymocytes. Medullary TECs (mTECs) facilitate the negative selection of self-reactive thymocytes and the differentiation of FOXP3+ regulatory T (Treg) cells2. Medullary TECs are also distinctive for their "promiscuous" gene expression, transcribing thousands of peripheral tissue genes (PTG) that are otherwise only expressed highly in one or two other organs. Much of this PTG expression by mTECs is controlled by the autoimmune regulator, AIRE. To determine the transcriptional impact of Kat7 loss, we purified mTECs and cTECs from Kat7-knockout and control mice and performed RNA-seq. The mTECs were further divided into MHCII-high and MHCII-low subsets. Overall design: cTEC, mTEC-high and mTEC-low populations were sorted from three biological replicates of wildtype mice and three biological replicates of Kat7 knockout mice to produce in 18 RNA-seq libraries in all. Sequencing was conducted on an Illumina NextSeq 500 to produce 75bp paired-end reads.