Normal mouse skin lacking Hras
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: David Quigley
PROVIDER: E-GEOD-60769 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Gene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as 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 extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. Refer to individual Series
2016-05-18 | E-GEOD-52650 | biostudies-arrayexpress
Project description:Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice.
2015-03-01 | GSE60769 | GEO
Project description:Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development1–3. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR-γ coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis. Mammary fat pads from 115 distinct untreated 8 week old [FVB/N x Spret/Ei] x FVB/N Backcross mice
2014-01-01 | E-GEOD-46077 | biostudies-arrayexpress
Project description:Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility. Keywords: Expression Quantitative Trait Loci A backcross was generated using male Mus spretus and female FVB/N mice; female F1 hybrids were mated with male FVB/N mice. Seventy-one backcross mice (8-12 weeks old) received a single dose of DMBA (25 µg per mouse in 200 µl acetone). Starting one week after the initiation tumors were promoted with TPA (200 µl of 10-4 M solution in acetone) twice weekly for 20 weeks. Initiation and promotion were performed on doral back skin. Normal tail skin was snap frozen when the animals were sacrificed. Tail epidermis from completely untreated Spretus, FVB, and Spretus x FVB F1 mice was also analyzed.
2008-12-31 | E-GEOD-12248 | biostudies-arrayexpress
Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. 60 carcinomas were harvested from 55 mice; five mice provided two carcinomas each.
2010-12-22 | E-GEOD-21247 | biostudies-arrayexpress
Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. Gene expression analysis was performed on mRNA extracted from 68 papillomas: two papillomas from each of 31 FVBBX mice and a single papilloma from six additional FVBBX mice. Papillomas were harvested when mice were sacrificed due to presence of a carcinoma or termination of the experiment.
2010-12-22 | E-GEOD-21263 | biostudies-arrayexpress
Project description:OVE26 (OVE) mice provide a useful model of advanced diabetic nephropathy (DN) with respect to albuminuria and pathologies. We showed that albuminuria, reduced GFR and interstitial fibrosis, which normally take 8-9 months to develop, are more advanced in uninephrectomized OVE mice within 10 weeks of surgery, at 4.5 months of age. The accelerated progression of renal damage, especially renal fibrosis in OVE-uni mice, was also identified at the gene expression level. The hepatic fibrosis/hepatic stellate cell activation pathway was by far the most significant Ingenuity canonical pathway identified by gene array in OVE-uni mice. Many inflammatory- and immune-related pathways were found among the top pathways up-regulated in OVE-uni kidneys, including acute-phase response signaling, leukocyte extravasation, IL6, IL10, IL12 signaling, TREM1 signaling, dendritic cell maturation and the complement system. These pathways were also dramatically up-regulated in 8-month-old OVE mice (GSE20636). Nephrectomized OVE mice are a much faster alternative model for studying advanced renal disease in diabetes. Study of renal gene expression in diabetic OVE26 mice. Uninephrectomy was used as an accelerating factor. Pooled RNA samples from 4 individual mice in each treatment group (OVE-uni, OVE-sham, FVB-uni, FVB-sham) were used for probe hybridization. Treatment groups: OVE-uni: uninephrectomy treatment in diabetic mice OVE-sham: sham surgery treatment in diabetic mice FVB-uni: uninephrectomy treatment in nondiabetic mice FVB-sham: sham surgery treatment in nondiabetic mice
2011-04-15 | E-GEOD-21448 | biostudies-arrayexpress
Project description:Gene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as 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 extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. Time course analysis of replicate exposure to epidermal application of TPA
2016-06-01 | E-GEOD-82067 | biostudies-arrayexpress
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-08 | PXD012506 | Pride
Project description:Modern omics technologies allow us obtaining global information on different types of biological networks. However, integrating these different types of analyzes into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially-defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS mediated signaling is the strongest from the plasma membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal new HRAS functions including the control of cell migration from the endoplasmic reticulum and p53 dependent cell survival when signaling from the Golgi apparatus.
2019-03-12 | E-MTAB-7672 | biostudies-arrayexpress