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Nat Immunol. 2015 Sep;16(9):933-41. doi: 10.1038/ni.3246. Epub 2015 Aug 3.

Single-cell transcriptome analysis reveals coordinated ectopic gene-expression patterns in medullary thymic epithelial cells.

Author information

1
1] Department of Genetics, Stanford University, School of Medicine, California, USA. [2] Stanford Genome Technology Center, Stanford University, California, USA.
2
European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
3
Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany.
4
1] Department of Genetics, Stanford University, School of Medicine, California, USA. [2] Stanford Genome Technology Center, Stanford University, California, USA. [3] European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.

Abstract

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 TRA expression in mTECs as a coordinated process that might involve local remodeling of chromatin and thus ensures a comprehensive representation of the immunological self.

PMID:
26237553
PMCID:
PMC4675844
DOI:
10.1038/ni.3246
[Indexed for MEDLINE]
Free PMC Article

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