Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator
Takahisa Miyao, Maki Miyauchi, S. Thomas Kelly, Tommy Terooatea, Tatsuya Ishikawa, Eugene Oh, Sotaro Hirai, Kenta Horie, Yuki Takakura, Houko Ohki, Mio Hayama, Yuya Maruyama, Takao Seki, Hiroto Ishii, Haruka Yabukami, Masaki Yoshida, Azusa Inoue, Asako Sakaue-Sawano, Atsushi Miyawaki, Masafumi Muratani, Aki Minoda, Nobuko Akiyama, Taishin Akiyama
Abstract
Medullary thymic epithelial cells (mTECs) are critical for self-tolerance induction in T cells via promiscuous expression of tissue-specific antigens (TSAs), which are controlled by the transcriptional regulator, AIRE. Whereas AIRE-expressing (Aire + ) mTECs undergo constant turnover in the adult thymus, mechanisms underlying differentiation of postnatal mTECs remain to be discovered. Integrative analysis of single-cell assays for transposase-accessible chromatin (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) suggested the presence of proliferating mTECs with a specific chromatin structure, which express high levels of Aire and co-stimulatory molecules, CD80 (Aire + CD80 hi ). Proliferating Aire + CD80 hi mTECs detected using Fucci technology express a minimal number of Aire-dependent TSAs and are converted into quiescent Aire + CD80 hi mTECs expressing high levels of TSAs after a transit amplification. These data provide evidence for the existence of transit-amplifying Aire + mTEC precursors during the Aire + mTEC differentiation process of the postnatal thymus.