Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from mouse liver tumor-initiating cells.

ABSTRACT: We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Goal and objectives: To study the requirement of HCV viral proteins and/or environmental factors (such as alcohol or obesity) in synergistic liver caner development in HCV Core or NS5A Tg mice given alcohol or high-cholesterol high-fat diet, mice were fed alcohol or high-cholesterol high-fat diet and liver tissues from these mice were examined for gene profiles. Alcohol or obesity contributes to synergistic tumor incidence and HCV Core or Ns5a-induced effects. Thus, analysis of gene profiling of these transgenic mice will identify the critical pathways to induce synergistic tumor formation caused by alcohol or obesity. Liver samples for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain gene profiling data in order to increase understanding the pathways. To perform gene array and proteomic analyses, mice were fed alcohol or high-cholesterol high-fat for 12 months and euthanized after 12 months feeding. Livers were collected at the time of euthanasia.

ORGANISM(S): Mus musculus

SUBMITTER: Keigo Machida

PROVIDER: E-GEOD-61435 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects One group of mice was fed an atherogenic high-fat (30% fat) diet containing cholic acid to increase fat uptake and another was fed a low-fat (6% fat) regular chow diet. Males and females from both diets were studied for mouse strains 129S1/SvImJ, A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, I/LnJ, MRL/MpJ-Tnfrsf6lpr/J, NZB/BINJ, PERA/Ei, and SM/J. All strains were sacrificed between 11- and 13 weeks of age except for CAST and PERA, which were harvested after 50 weeks of age. CAST and PERA were subsequently removed from our analysis based on discrepant harvest age, but can be found in our database (see below). Three replicate animals were used for each combination of diet, strain, and sex, resulting in a total of 120 mice surveyed for gene expression.

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Expression data from mouse liver tumor-initiating cells.

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