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Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer

Quigley, David A; Kandyba, Eve; Huang, Phillips; Halliwill, Kyle D; Sjölund, Jonas LU ; Pelorosso, Facundo; Wong, Christine E; Hirst, Gillian L; Wu, Di and Delrosario, Reyno, et al. (2016) In Cell Reports 16(4). p.65-1153
Abstract

Inherited 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... (More)

Inherited 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.

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Cell Reports
volume
16
issue
4
pages
13 pages
publisher
Cell Press
external identifiers
  • Scopus:84978804163
ISSN
2211-1247
DOI
10.1016/j.celrep.2016.06.061
language
English
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yes
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7bc60763-d682-4a89-9447-06f1d4af4dc0
date added to LUP
2016-09-08 12:41:54
date last changed
2016-10-13 05:13:21
@misc{7bc60763-d682-4a89-9447-06f1d4af4dc0,
  abstract     = {<p>Inherited 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.</p>},
  author       = {Quigley, David A and Kandyba, Eve and Huang, Phillips and Halliwill, Kyle D and Sjölund, Jonas and Pelorosso, Facundo and Wong, Christine E and Hirst, Gillian L and Wu, Di and Delrosario, Reyno and Kumar, Atul and Balmain, Allan},
  issn         = {2211-1247},
  language     = {eng},
  month        = {07},
  number       = {4},
  pages        = {65--1153},
  publisher    = {ARRAY(0xd4f6a00)},
  series       = {Cell Reports},
  title        = {Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.06.061},
  volume       = {16},
  year         = {2016},
}