セキ　タカオ   Seki Takao   関　崇生    所属   東邦大学  医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Integrative analysis of scRNA- seq and scATAC- seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator
掲載誌名	正式名：eLife
掲載区分	国外
出版社	eLife Sciences Publications Ltd
巻・号・頁	11(e73998)
著者・共著者	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
発行年月	2022/05/17
概要	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.