title: Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism.
abstract: Promiscuous expression of tissue-restricted autoantigens in medullary thymic epithelial cells (mTECs) imposes central T cell tolerance. The molecular regulation of this unusual gene expression is not understood, in particular its delineation from cell lineage-specific gene expression control remains unclear. Here, we compared the expression profile of the casein gene locus in mTECs and mammary gland epithelial cells by single cell PCR. Mammary gland cells showed highly correlated intra- and interchromosomal coexpression of milk proteins (the casein genes, lactalbumin-alpha and whey acidic protein) and one of its transcriptional regulators (Elf5). In contrast, coexpression of these genes in mature CD80(hi) mTECs was rarely observed and no pattern of gene expression in individual mTECs was discernible. The apparent stochastic expression pattern of genes within the casein locus, the lower mRNA levels compared with mammary gland cells in conjunction with frequent coexpression of insulin in single mTECs clearly delineates the molecular mechanism(s) of promiscuous gene expression from cell lineage-specific gene control.
authors.affiliation: Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Derbinski
authors.forename: Sheena
authors.initials: S
authors.lastname: Pinto
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rösch
authors.forename: Klaus
authors.initials: K
authors.lastname: Hexel
authors.forename: Bruno
authors.initials: B
authors.lastname: Kyewski
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis; D002364:Caseins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007768:Lactalbumin / Q000378:metabolism; D007774:Lactation; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008894:Milk Proteins / Q000378:metabolism; D013269:Stochastic Processes; D013950:Thymus Gland / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D002364:Caseins; D008894:Milk Proteins; C024471:whey acidic proteins; D007768:Lactalbumin