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

Elife. 2022 May 17;11:e73998. doi: 10.7554/eLife.73998.

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 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.

Keywords: AIRE; ATAC; differentiation; immunology; inflammation; mouse; single-cell analysis; thymic epithelial cells; transit-amplifying cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Chromatin* / metabolism
  • Epithelial Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Single-Cell Analysis*
  • Thymus Gland
  • Transposases / metabolism

Substances

  • Chromatin
  • Transposases

Associated data

  • GEO/GSE103967
  • GEO/GSE107910
  • GEO/GSE137699

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.