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Derivation of marker gene signatures from human skin and their use in the interpretation trancriptional changes associated with dermatological disorders

Shih, BB-J; Nirmal, AJ; Headon, DJ; Akbar, AN; Mabbott, NA; Freeman, TC; (2016) Derivation of marker gene signatures from human skin and their use in the interpretation trancriptional changes associated with dermatological disorders. The Journal of Pathology , 241 (5) pp. 600-613. 10.1002/path.4864. Green open access

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Abstract

Numerous studies have explored the altered transcriptional landscape associated with skin diseases to understand the nature of these disorders. However, data interpretation represents a significant challenge due to a lack of good maker sets for many of the specialised cell types that make up this tissue, whose composition may fundamentally alter during disease. Here we have sought to derive expression signatures that define the various cell types and structures that make up human skin, and demonstrate how they can be used to aid the interpretation of transcriptomic data derived from this organ. Two large normal skin transcriptomics datasets were identified, one RNA-seq (n = 578), the other microarray (n = 165), quality controlled and subjected separately to network-based analyses to identify clusters of robustly co-expressed genes. The biological significance of these clusters was then assigned using a combination of bioinformatics analyses, literature and expert review. After cross comparison between analyses, 20 gene signatures were defined. These include expression signatures for hair follicles, glands (sebaceous, sweat, apocrine), keratinocytes, melanocytes, endothelia, muscle, adipocytes, immune cells, and a number of pathway systems. Collectively we have named this resource SkinSig. SkinSig was then used in the analysis of transcriptomic datasets for 18 skin conditions, providing in-context interpretation of these data. For instance, conventional analysis has shown there to be a decrease in keratinisation and fatty metabolism with age; we more accurately define these changes to be due to loss of hair follicles and sebaceous glands. SkinSig also highlighted the over-/under-representation of various cell types in skin diseases, reflecting an influx in immune cells in inflammatory disorders and a relative reduction in other cell types. Overall, our analyses demonstrate the value of this new resource in defining the functional profile of skin cell types and appendages, and in improving the interpretation of disease data.

Type: Article
Title: Derivation of marker gene signatures from human skin and their use in the interpretation trancriptional changes associated with dermatological disorders
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/path.4864
Publisher version: http://dx.doi.org/10.1002/path.4864
Language: English
Additional information: © 2016 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Transcriptomics, gene expression, skin, sebaceous gland, apocrine gland, sweat gland, psoriasis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1537645
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