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

Akiyama, T.; MIyao, T.; Miyauchi, M.; Kelly, T.; Terooatea, T. W.; Ishikawa, T.; Oh, E.; Hirai, S.; Horie, K.; Takakura, Y.; Ohki, H.; Hayama, M.; Maruyama, Y.; Seki, T.; Yabukami, H.; Yoshida, M.; Inoue, A.; Sakaue-Sawano, A.; Miyawaki, A.; Minoda, A.; Akiyama, N.

doi:10.1101/2021.10.04.463004

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bioRxiv · 10.1101/2021.10.04.463004

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

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Abstract

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.

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Akiyama, T., MIyao, T., Miyauchi, M., Kelly, T., Terooatea, T. W., Ishikawa, T., Oh, E., Hirai, S., Horie, K., Takakura, Y., Ohki, H., Hayama, M., Maruyama, Y., Seki, T., Yabukami, H., Yoshida, M., Inoue, A., Sakaue-Sawano, A., Miyawaki, A., Minoda, A., Akiyama, N.. 2021-10-05. Integrative analysis of scRNAs-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator. https://doi.org/10.1101/2021.10.04.463004

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