Journal
NATURE IMMUNOLOGY
Volume 16, Issue 9, Pages 933-941Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3246
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Funding
- European Union
- Helmholtz Center
- Sonderforschungsbereich (DFG 938)
- European Research Council [ERC-2012-AdG]
- US National Institutes of Health [P01 HG000205, R01 GM068717]
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Expression of tissue-restricted self antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential for the induction of self-tolerance and prevents autoimmunity, with each TRA being expressed in only a few mTECs. How this process is regulated in single mTECs and is coordinated at the population level, such that the varied single-cell patterns add up to faithfully represent TRAs, is poorly understood. Here we used single-cell RNA sequencing and obtained evidence of numerous recurring TRA-co-expression patterns, each present in only a subset of mTECs. Co-expressed genes clustered in the genome and showed enhanced chromatin accessibility. Our findings characterize IRA expression in mTECs as a coordinated process that might involve local remodeling of chromatin and thus ensures a comprehensive representation of the immunological self.
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