Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer
| Autor: | Eve Kandyba, David A. Quigley, Jonas Sjölund, Reyno Delrosario, Di Wu, Phillips Y. Huang, Gillian L. Hirst, Kyle D. Halliwill, Atul Kumar, Christine E. Wong, Facundo G. Pelorosso, Allan Balmain |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell signaling Skin Neoplasms Tumor suppressor gene Carcinogenesis Quantitative Trait Loci Medical Physiology Gene regulatory network Gene Expression medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences Genetic Gene expression Genetics medicine Animals 2.1 Biological and endogenous factors Genetic Predisposition to Disease Gene Regulatory Networks Polymorphism Aetiology Sonic hedgehog lcsh:QH301-705.5 Skin Cancer Inflammation Polymorphism Genetic biology Inflammatory and immune system Wnt signaling pathway Stem Cell Research Cell biology Germ Cells 030104 developmental biology lcsh:Biology (General) Expression quantitative trait loci Disease Progression biology.protein Stem Cell Research - Nonembryonic - Non-Human Biochemistry and Cell Biology Signal Transduction Biotechnology |
| Zdroj: | Cell reports, vol 16, iss 4 Cell Reports, Vol 16, Iss 4, Pp 1153-1165 (2016) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.06.061 |
| Popis: | SummaryInherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. |
| Databáze: | OpenAIRE |
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