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

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 thym...

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Published in:eLife 2022-05, Vol.11
Main Authors: MIyao, Takahisa, Miyauchi, Maki, Kelly, S Thomas, Terooatea, Tommy W, Ishikawa, Tatsuya, Oh, Eugene, Hirai, Sotaro, Horie, Kenta, Takakura, Yuki, Ohki, Houko, Hayama, Mio, Maruyama, Yuya, Seki, Takao, Ishii, Hiroto, Yabukami, Haruka, Yoshida, Masaki, Inoue, Azusa, Sakaue-Sawano, Asako, Miyawaki, Atsushi, Muratani, Masafumi, Minoda, Aki, Akiyama, Nobuko, Akiyama, Taishin
Format: Article
Language:English
Subjects:
AIRE
AIRE protein
Animals
Antigens
Approximation
ATAC
CD80 antigen
Cell cycle
Cell Differentiation - genetics
Chromatin
Chromatin - metabolism
differentiation
Epithelial cells
Epithelial Cells - metabolism
Experiments
Gene expression
Immunological tolerance
Immunology and Inflammation
Lymphocytes
Lymphocytes T
Mice
Mice, Inbred C57BL
Population
Single-Cell Analysis
Stem cells
thymic epithelial cells
Thymus
Thymus Gland
transit-amplifying cells
Transposase
Transposases - metabolism
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Summary: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 ). Proliferating Aire CD80 mTECs detected using Fucci technology express a minimal number of Aire-dependent TSAs and are converted into quiescent Aire CD80 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.73998