PT  - JOURNAL ARTICLE
AU  - Takahisa Miyao
AU  - Maki Miyauchi
AU  - S. Thomas Kelly
AU  - Tommy W. Terooatea
AU  - Tatsuya Ishikawa
AU  - Eugene Oh
AU  - Sotaro Hirai
AU  - Kenta Horie
AU  - Yuki Takakura
AU  - Houko Ohki
AU  - Mio Hayama
AU  - Yuya Maruyama
AU  - Takao Seki
AU  - Haruka Yabukami
AU  - Masaki Yoshida
AU  - Azusa Inoue
AU  - Asako Sakaue-Sawano
AU  - Atsushi Miyawaki
AU  - Masafumi Muratani
AU  - Aki Minoda
AU  - Nobuko Akiyama
AU  - Taishin Akiyama
TI  - Integrative analysis of scRNAs-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator
AID  - 10.1101/2021.10.04.463004
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.04.463004
4099  - http://biorxiv.org/content/early/2021/10/05/2021.10.04.463004.short
4100  - http://biorxiv.org/content/early/2021/10/05/2021.10.04.463004.full
AB  - 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 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 by using Fucci technology express a minimal level 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 Aire+mTEC differentiation process of the postnatal thymus.Competing Interest StatementThe authors have declared no competing interest.