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Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling.

ABSTRACT: To increase our understanding of skin, it is important to define the molecular constituents of the cell types and epidermal layers that signify normal skin. We have combined a genome-wide transcriptomics analysis, using deep sequencing of mRNA from skin biopsies, with immunohistochemistry-based protein profiling to characterize the landscape of gene and protein expression in normal human skin. The transcriptomics and protein expression data of skin were compared to 26 (RNA) and 44 (protein) other normal tissue types. All 20,050 putative protein-coding genes were classified into categories based on patterns of expression. We found that 417 genes showed elevated expression in skin, with 106 genes expressed at least five-fold higher than that in other tissues. The 106 genes categorized as skin enriched encoded for well-known proteins involved in epidermal differentiation and proteins with unknown functions and expression patterns in skin, including the C1orf68 protein, which showed the highest relative enrichment in skin. In conclusion, we have applied a genome-wide analysis to identify the human skin-specific proteome and map the precise localization of the corresponding proteins in different compartments of the skin, to facilitate further functional studies to explore the molecular repertoire of normal skin and to identify biomarkers related to various skin diseases.

SUBMITTER: Edqvist PH

PROVIDER: S-EPMC4305515 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling.

Edqvist Per-Henrik D PH Fagerberg Linn L Hallström Björn M BM Danielsson Angelika A Edlund Karolina K Uhlén Mathias M Pontén Fredrik F

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20141119 2

To increase our understanding of skin, it is important to define the molecular constituents of the cell types and epidermal layers that signify normal skin. We have combined a genome-wide transcriptomics analysis, using deep sequencing of mRNA from skin biopsies, with immunohistochemistry-based protein profiling to characterize the landscape of gene and protein expression in normal human skin. The transcriptomics and protein expression data of skin were compared to 26 (RNA) and 44 (protein) othe ...[more]

PMID: 25411189

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Project description:The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correlation revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to TGFbeta-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFb and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodeling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling. Experiment Overall Design: In this (Zürich) data set three melanocyte cultures and twelve melanoma cultures were analyzed.

Dataset Information

Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling.

Publications

Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling.

Similar Datasets

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