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.

Chromosome conformation and gene expression patterns differ profoundly in human fibroblasts grown in spheroids versus monolayers

“…However, the increased expression of 111 genes related to cell differentiation suggests fibroblasts grown in 3D may transition toward a more differentiated state compared with the more proliferating state in 2D. A comparison to the top 50 skin-specific genes from previously published work 17 showed a trend of higher expression of skin-specific genes (23 out of 50) in 3D cells relative to 2D cells. For the remaining 27 genes, 17 were not detected in our samples, and 10 showed lower expression levels in the 3D samples.…”

“…A recent study of gene expression profiles in human tissues by Edqvist et al identified 106 skinspecific genes known to be involved in skin development and differentiation. 17 Comparing the top 50 skin-specific genes available from this publication, we found that in both 3D and 2D samples, 17 of them were not detectable at the current sequencing depth, 30 genes were expressed at low levels (FPKM < 1) either in 3D or 2D cells, and 3 genes were called expressed. All 3 expressed genes (ASPRV1, KRT10, and SERPINB7) showed increased expression levels in 3D cells relative to 2D cells.…”

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

“…The tissues with the most mRNAs highly enriched (at least 5× the levels in all other tissues) are testis (999) and brain (318). Several tissue-specific HPA publications have been published, and more are expected during 2015 with tissue-specific immunohistochemical and transcript evidence to guide specimen selection for further MS studies, for example, describing the brain, 18 liver, 19 testis, 20 kidney, 21 pancreas, 22 skin, 23 adipose tissue, 24 gallbladder, 25 lung, 26 gastrointestinal tract, 27 and cardiac and skeletal muscle. 28 HPA, v14, will be released in Fall 2015 along with a novel Rodent Brain Atlas comprising immunofluorescently stained whole-mouse-brain sections.…”

The Human Protein Atlas – an important resource for basic and clinical research

“…This allows for analysis of protein expression with a spatial distribution, in the context of neighboring cells. The unique combination of transcriptomics with antibody-based proteomics allows for identification of protein selectively expressed in a certain cell type, such as pneumocytes or macrophages in lung [8], or different layers of epidermis in skin [9], which aids in further understanding of the nature of the protein. In-depth studies of genes elevated in a certain tissue under normal conditions also provide the basis for disease-specific research, as it can be anticipated that these genes play an important role in the organ physiology.…”

“…More detailed exploration of Human Protein Atlas images not only applies to stromal cells, but also groups of cells that are already analyzed in the present setup, but could be scored with a higher resolution. Examples include differential protein expression in various layers of epidermis in normal skin [9], or proteins exclusively expressed in type I or type II pneumocytes in lung [8].…”