This SuperSeries is composed of the SubSeries listed below.
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesPAX8-PPARG fusion protein (PPFP) results from a t(2;3)(q13;p25) chromosomal translocation, is found in 30% of follicular thyroid carcinomas, and demonstrates oncogenic capacity in transgenic mice. A PPARG ligand, pioglitazone, is highly therapeutic in mice with PPFP thyroid carcinoma. We used our previously characterized transgenic mouse model of PPFP thyroid carcinoma to identify PPFP binding sites in vivo using ChIP-seq, and to identify genes and pathways regulated by PPFP with and without pioglitazone treatment via integration with RNA-seq and Affymetrix microarray data. This submission contains the Affymetrix microarray data. PPFP and pioglitazone regulated genes involved in lipid and fatty acid metabolism, ribosome function, immune processes, cell death and other cancer-related processes. The RNA-seq data yielded similar findings.
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesLong noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health.
The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesThe objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesThe objective of this study was to determine common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. There were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; there were few genes in common between any of the line-pairs in these categories and networks. The overall ANOVAs of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. Ingenuity analysis revealed (a) several significant networks with clusters of genes associated with App, Egfr, Ccnd1, Itga2b, Rxra and Vcl; and (b) changes in genes within networks associated with dopamine, the glutamate synapse, Nfkb signaling, IL pathways and integrin. There were 22 genes that were significantly different in the overall ANOVA and were significantly different (in the direction) in at least 3 line-pairs, e.g., Crebl2, Gsta4, Itga9 & Itg2. In conclusion, the findings suggest that (a) different innate mechanisms may be contributing to vulnerability to high alcohol drinking behavior among the selectively bred lines, and (b) small contributions in expression of multiple genes within certain transmitter systems and intracellular signaling pathways may contribute to the disparate alcohol drinking characteristics of the 5 line-pairs.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesThe objective of this study was to determine common innate differences in gene expression in the Central Nucleus of the Amygdala (CeA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesAdipose tissue stromal cells contribute to the regulation of adipose tissue in lean and obese states. Myeloid cells such as adipose tissue macrophages (ATMs) and dendritic cells (ATDCs) undergo both quantitative and qualitative changes with obesity. Due to similarity in markers the identify of adipose tissue dendritic cells and macrophages has been elusive. We have refined prior protocols to unambiguously discern ATM and ATDC in mice. We used microarrays to compare the profiles of ATMs and ATDC from gonadal adipose tissue from lean, obese, and formerly obese mice. We also isolated preadipocytes (PA) from lean and obese mice for comparison.
Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.
Sex, Specimen part
View SamplesIntroduction: Though heavy alcohol drinking has been well characterized as causing a variety of injuries, recent epidemiological evidence in humans suggests moderate consumption may provide beneficial effects. For example, there exists a J- or U-shaped relationship between the level of alcohol intake and cardiovascular disease risk. We investigated the underlying mechanisms of these positive consequences by identifying which genes are responsive to moderate alcohol intake in the liver, the primary site for alcohol metabolism. Methods: Twelve female, inbred, alcohol-preferring (iP10a) rats were split equally between chronic water exposure and voluntary chronic ethanol exposure. Hepatic cholesterol and triglyceride levels were analyzed both histologically and biochemically. Hepatic transcriptomes were paired-end sequenced on the Illumina HiScanSQ system. Reads were analyzed and mapped using CLCbio Genomics Workbench 4.9. We confirmed altered expression of a subset of genes using TaqMan-based qRT-PCR. To quantify DNA methylation, we first digested DNA with methylation sensitive restriction enzymes and then performed qPCR using TaqMan assays surrounding the digest sites. Calculating ?Ct between a mock digest and digest determines the percent methylation in that locus. Results: Voluntary alcohol consumption in iP10a rats modeled moderate consumption in humans. These levels did not result in intrahepatic fat accumulation. Sequencing produced ~1.2 Gb of sequence per sample, and 65% of reads mapped uniquely. Using a FDR corrected p value of 0.05 we found 250 altered transcripts. Ontology analysis of genes with a fold change =1.3 identified many cholesterol synthesis genes and cytoskeleton subunit genes, all of which were down-regulated. Of the 28 genes reanalyzed by qRT-PCR, altered expression was confirmed in 24 genes including the majority of the cholesterol synthesis and cytoskeleton subunit genes. Lastly, we profiled methylation throughout the promoter and gene body of four genes elicited in the RNA-Seq experiment. We found that alcohol caused demethylation at all loci; however this loss happened in a site-specific, tightly regulated manner. Conclusion: Voluntary consumption in the iP10a animals models moderate consumption in humans, does not produce intrahepatic fat accumulation, and causes down-regulation of a majority of cholesterol synthesis genes. Moderate alcohol also results in a tightly-regulated demethylation effect. Our results explain, at least in part, the J- or U-shaped relationship between level of alcohol intake and cardiovascular disease risk. Overall design: We sequenced 12 female iP10a rat hepatic transcriptomes providing 6 biological replicates for water control and 6 for ethanol treatment.
A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.
No sample metadata fields
View SamplesWe performed RNA sequencing analysis of hepatic gene expression a few hours after amlexanox treatment, and identified over 1700 differentially expressed genes. Pathway analysis of these differentially regulated genes revealed that the top two most enriched pathways were the adipocytokine signaling pathway and the Jak-STAT signaling pathway. Overall design: RNA-seq analysis of hepatic gene expression was used to identify differentially expressed genes in response to Amlexanox treatment.
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
No sample metadata fields
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