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Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters.

Gotter J, Brors B, Hergenhahn M, Kyewski B - J. Exp. Med. (2004)

Bottom Line: Analysis of promiscuous gene expression in purified stromal cells of the human thymus at the single and global gene level documents the species conservation of this phenomenon.Although there are no apparent structural or functional commonalities among these genes and their products, they cluster along chromosomes.These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.

ABSTRACT
Promiscuous expression of tissue-specific self-antigens in the thymus imposes T cell tolerance and protects from autoimmune diseases, as shown in animal studies. Analysis of promiscuous gene expression in purified stromal cells of the human thymus at the single and global gene level documents the species conservation of this phenomenon. Medullary thymic epithelial cells overexpress a highly diverse set of genes (>400) including many tissue-specific antigens, disease-associated autoantigens, and cancer-germline genes. Although there are no apparent structural or functional commonalities among these genes and their products, they cluster along chromosomes. These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression.

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Related in: MedlinePlus

Comparative global gene expression in thymic stromal cells. The relative expression levels as detected by gene arrays are depicted as scatter plots of two experiments (blue and red). (a) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in cTECs. (b) Signal strength of genes present or marginally present in cTECs in both comparisons and present, marginally present, or absent in mTECs. (c) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in DCs. Note the higher proportion of genes specific for mTECs (absent in cTECs) and their low expression levels. (d) Quantitative analysis of relative gene expression in mutual comparisons between cTECs, mTECs, DCs, and mature thymocytes. Numbers above bars denote the frequency of genes overexpressed in each case. The gene pool overexpressed in mTECs versus cTECs (red bar) has been analyzed in more detail. For details of calculations, see Materials and Methods. TC, thymocytes.
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fig3: Comparative global gene expression in thymic stromal cells. The relative expression levels as detected by gene arrays are depicted as scatter plots of two experiments (blue and red). (a) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in cTECs. (b) Signal strength of genes present or marginally present in cTECs in both comparisons and present, marginally present, or absent in mTECs. (c) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in DCs. Note the higher proportion of genes specific for mTECs (absent in cTECs) and their low expression levels. (d) Quantitative analysis of relative gene expression in mutual comparisons between cTECs, mTECs, DCs, and mature thymocytes. Numbers above bars denote the frequency of genes overexpressed in each case. The gene pool overexpressed in mTECs versus cTECs (red bar) has been analyzed in more detail. For details of calculations, see Materials and Methods. TC, thymocytes.

Mentions: We performed a comparison of the gene expression profiles of cTECs, mTECs, DCs, and mature thymocytes. RNA was isolated from independent replicates of each subset, and amplified cDNA were prepared by two rounds of cDNA synthesis and in vitro transcription steps and hybridized to GeneChip® oligonucleotide arrays (Affymetrix U95Av2) containing ∼12,500 probe sets. Scanned arrays were analyzed with Affymetrix software Microarray Suite 5.0 to identify cell type-specific gene expression profiles and assess quantitative difference in gene expression among these subsets. Calculation of the fold change in gene expression was based on the Lower Confidence Bound as a measure of enrichment of gene expression. Genes for which the signal log ratio low was ≥1 (equal to a difference of at least twofold) and which at the same time were designated increased or marginally increased were considered (see Materials and Methods). Comparisons were performed among the different cell subsets within each experiment, and only genes fulfilling these criteria in both comparisons were considered (Fig. 3 , a–c).


Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters.

Gotter J, Brors B, Hergenhahn M, Kyewski B - J. Exp. Med. (2004)

Comparative global gene expression in thymic stromal cells. The relative expression levels as detected by gene arrays are depicted as scatter plots of two experiments (blue and red). (a) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in cTECs. (b) Signal strength of genes present or marginally present in cTECs in both comparisons and present, marginally present, or absent in mTECs. (c) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in DCs. Note the higher proportion of genes specific for mTECs (absent in cTECs) and their low expression levels. (d) Quantitative analysis of relative gene expression in mutual comparisons between cTECs, mTECs, DCs, and mature thymocytes. Numbers above bars denote the frequency of genes overexpressed in each case. The gene pool overexpressed in mTECs versus cTECs (red bar) has been analyzed in more detail. For details of calculations, see Materials and Methods. TC, thymocytes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211762&req=5

fig3: Comparative global gene expression in thymic stromal cells. The relative expression levels as detected by gene arrays are depicted as scatter plots of two experiments (blue and red). (a) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in cTECs. (b) Signal strength of genes present or marginally present in cTECs in both comparisons and present, marginally present, or absent in mTECs. (c) Signal strength of genes present or marginally present in mTECs in both comparisons and present, marginally present, or absent in DCs. Note the higher proportion of genes specific for mTECs (absent in cTECs) and their low expression levels. (d) Quantitative analysis of relative gene expression in mutual comparisons between cTECs, mTECs, DCs, and mature thymocytes. Numbers above bars denote the frequency of genes overexpressed in each case. The gene pool overexpressed in mTECs versus cTECs (red bar) has been analyzed in more detail. For details of calculations, see Materials and Methods. TC, thymocytes.
Mentions: We performed a comparison of the gene expression profiles of cTECs, mTECs, DCs, and mature thymocytes. RNA was isolated from independent replicates of each subset, and amplified cDNA were prepared by two rounds of cDNA synthesis and in vitro transcription steps and hybridized to GeneChip® oligonucleotide arrays (Affymetrix U95Av2) containing ∼12,500 probe sets. Scanned arrays were analyzed with Affymetrix software Microarray Suite 5.0 to identify cell type-specific gene expression profiles and assess quantitative difference in gene expression among these subsets. Calculation of the fold change in gene expression was based on the Lower Confidence Bound as a measure of enrichment of gene expression. Genes for which the signal log ratio low was ≥1 (equal to a difference of at least twofold) and which at the same time were designated increased or marginally increased were considered (see Materials and Methods). Comparisons were performed among the different cell subsets within each experiment, and only genes fulfilling these criteria in both comparisons were considered (Fig. 3 , a–c).

Bottom Line: Analysis of promiscuous gene expression in purified stromal cells of the human thymus at the single and global gene level documents the species conservation of this phenomenon.Although there are no apparent structural or functional commonalities among these genes and their products, they cluster along chromosomes.These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.

ABSTRACT
Promiscuous expression of tissue-specific self-antigens in the thymus imposes T cell tolerance and protects from autoimmune diseases, as shown in animal studies. Analysis of promiscuous gene expression in purified stromal cells of the human thymus at the single and global gene level documents the species conservation of this phenomenon. Medullary thymic epithelial cells overexpress a highly diverse set of genes (>400) including many tissue-specific antigens, disease-associated autoantigens, and cancer-germline genes. Although there are no apparent structural or functional commonalities among these genes and their products, they cluster along chromosomes. These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression.

Show MeSH
Related in: MedlinePlus