Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator

eLife

Tommy W Terooatea¹  Hiroto Ishii¹  Masaki Yoshida¹  Kenta Horie¹  Maki Miyauchi¹  Aki Minoda¹  Asako Sakaue-Sawano¹  Eugene Oh²  Tatsuya Ishikawa²  Nobuko Akiyama²  Yuki Takakura³  Atsushi Miyawaki³  Masafumi Muratani³  Sotaro Hirai³  Azusa Inoue³  S Thomas Kelly³  Houko Ohki³  Yuya Maruyama³  Takahisa Miyao³  Takao Seki³  Haruka Yabukami³  Mio Hayama³  Taishin Akiyama⁴ 

[1] Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan;Laboratory for Cellular Epigenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan;Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan;YCI Laboratory for Immunological Transcriptomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;

关键词: thymic epithelial cells;    AIRE;    differentiation;    single-cell analysis;    ATAC;    transit-amplifying cells;   

DOI  :  10.7554/eLife.73998

来源: DOAJ

【 摘 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.

【 授权许可】

Unknown