Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator
oleh: Takahisa Miyao, Maki Miyauchi, S Thomas Kelly, Tommy W 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
| Format: | Article |
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| Diterbitkan: | eLife Sciences Publications Ltd 2022-05-01 |
Deskripsi
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+CD80hi). Proliferating Aire+CD80hi mTECs detected using Fucci technology express a minimal number of Aire-dependent TSAs and are converted into quiescent Aire+CD80hi 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.