title: Single-cell transcriptome analysis reveals coordinated ectopic gene-expression patterns in medullary thymic epithelial cells.
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.
authors.affiliation: 1] Department of Genetics, Stanford University, School of Medicine, California, USA. [2] Stanford Genome Technology Center, Stanford University, California, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Brennecke
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Reyes
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Sheena
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Rattay
authors.affiliation: 1] Department of Genetics, Stanford University, School of Medicine, California, USA. [2] Stanford Genome Technology Center, Stanford University, California, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Küchler
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
authors.forename: Wolfgang
authors.identifier: 0000000204742218
authors.initials: W
authors.lastname: Huber
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Kyewski
authors.affiliation: 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.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D015551:Autoimmunity / Q000276:immunology; D042002:Chromatin Assembly and Disassembly; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*; D059010:Single-Cell Analysis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger