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

First Author  Miyao T Year  2022
Journal  Elife Volume  11
PubMed ID  35578835 Mgi Jnum  J:325655
Mgi Id  MGI:7280373 Doi  10.7554/eLife.73998
Citation  MIyao T, et al. (2022) Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator. Elife 11:e73998
abstractText  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(hi)). Proliferating Aire(+)CD80(hi) mTECs detected using Fucci technology express a minimal number of Aire-dependent TSAs and are converted into quiescent Aire(+)CD80(hi) 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.
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