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GSE14340
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The expression profiles of five human trunk level neural crest cell lines were determined on Affymetrix chips HG U133 Plus 2.0.
Publication Title
Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Murine 11K SubA Array (mu11ksuba)
Description
The expression of adipogenic genes is decreased in obesity and diabetes mellitus
Publication Title
The expression of adipogenic genes is decreased in obesity and diabetes mellitus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistant. We used DNA microarrays and RT-PCR to compare the gene expression in BTBR-ob/ob versus B6-ob/ob mice in adipose tissue, liver, skeletal muscle, and pancreatic islets. Our results show: 1) there is an increased expression of genes involved in inflammation in adipose tissue of diabetic mice; 2) lipogenic gene expression was lower in adipose tissue of diabetes-susceptible mice, and it continued to decrease with the development of diabetes, compared with diabetes-resistant obese mice; 3) hepatic expression of lipogenic enzymes was increased and the hepatic triglyceride content was greatly elevated in diabetes-resistant obese mice; 4) hepatic expression of gluconeogenic genes was suppressed at the prediabetic stage but not at the onset of diabetes; and 5) genes normally not expressed in skeletal muscle and pancreatic islets were expressed in these tissues in the diabetic mice. We propose that increased hepatic lipogenic capacity protects the B6-ob/ob mice from the development of type 2 diabetes. Diabetes 52:688700, 2003
Publication Title
Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The following abstract from the submitted manuscript describes the major findings of this work.
Publication Title
A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
Illumina HiSeq 2500
Description
Abstract: Histones are small proteins that form the core of nucleosomes, around which eukaryotic DNA wraps to ultimately form the highly organized and compressed structure known as chromatin. The N-terminal tails of histones are highly modified, and the modification state of these proteins dictates whether chromatin is permissive or repressive to processes that require physical access to DNA, including transcription and DNA replication and repair. The enzymes that add and remove histone modifications are known to be exquisitely sensitive to endogenous small molecule metabolite availability. In this manner, chromatin can adapt to changes in environment, particularly diet-induced metabolic state. Importantly, gut microbiota contribute to robust host metabolic phenotypes, and produce a myriad of metabolites that are detectable in host circulation. Further, gut microbial community composition and metabolite production are regulated by host diet, as a major source of carbon and energy for the microbiota. While prior studies have reported robust host metabolic associations with gut microbiota, the mechanisms therein remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues including colon, adipose tissue, and liver. This regulatory relationship is altered by diet: a “Western-type” diet leads to a general suppression of the microbiota-dependent chromatin changes observed in a polysaccharide rich diet. Finally, we demonstrate that supplementation of germ-free mice with major products of gut bacterial fermentation (i.e., short-chain fatty acids acetate, propionate, and butyrate) is sufficient to recapitulate many of the effects of colonization on host epigenetic states. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health. Overall design: 15 samples in total (biological n=3 per for each of 5 conditions; 19kw old male C57BL/6J mouse liver): (1) GF mouse liver on chow diet, (2) ConvR mouse liver on chow diet, (3) ConvD mouse liver on chow diet, (4) GF mouse liver on HF/HS diet, (5) ConvR mouse liver on HF/HS diet
Publication Title
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Murine Genome U74A Array (mgu74a)
Description
Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
Publication Title
Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Abstract: Histones are small proteins that form the core of nucleosomes, around which eukaryotic DNA wraps to ultimately form the highly organized and compressed structure known as chromatin. The N-terminal tails of histones are highly modified, and the modification state of these proteins dictates whether chromatin is permissive or repressive to processes that require physical access to DNA, including transcription and DNA replication and repair. The enzymes that add and remove histone modifications are known to be exquisitely sensitive to endogenous small molecule metabolite availability. In this manner, chromatin can adapt to changes in environment, particularly diet-induced metabolic state. Importantly, gut microbiota contribute to robust host metabolic phenotypes, and produce a myriad of metabolites that are detectable in host circulation. Further, gut microbial community composition and metabolite production are regulated by host diet, as a major source of carbon and energy for the microbiota. While prior studies have reported robust host metabolic associations with gut microbiota, the mechanisms therein remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues including colon, adipose tissue, and liver. This regulatory relationship is altered by diet: a “Western-type” diet leads to a general suppression of the microbiota-dependent chromatin changes observed in a polysaccharide rich diet. Finally, we demonstrate that supplementation of germ-free mice with major products of gut bacterial fermentation (i.e., short-chain fatty acids acetate, propionate, and butyrate) is sufficient to recapitulate many of the effects of colonization on host epigenetic states. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health. Overall design: 9 samples in total (biological n=3 per for each of 3 conditions; 14kw old male C57BL/6J mouse liver): (1) GF mouse liver on chow diet, (2) ConvD mouse liver on chow diet, (3) GF mouse liver on chow diet + supplemented drinking water with short chain fatty acids
Publication Title
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. To map gene regulatory pathways, we used microarray-derived gene expression measurements in 60 individuals of an F2 sample segregating for diabetes. We performed correlation analysis among ~40,000 expression traits. By combining correlation among expression traits and linkage mapping information, we were able to identify regulatory networks, make functional predictions to uncharacterized genes, and characterize novel members of known pathways. Using 36 seed traits, we found evidence of coordinate regulation of 160 G-protein coupled receptor (GPCR) pathway expression traits. Of the 160 traits, 50 had their major LOD peak within 8 cM of a locus on chromosome 2, and 81 others had a secondary peak in this region. A previously uncharacterized Riken cDNA clone, which showed strong correlation with stearoyl CoA desaturase 1 expression, was experimentally validated to be responsive to conditions that regulate lipid metabolism. Using linkage mapping, we identified multiple genes whose expression is under the control of transcription regulatory loci. Trait-correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we only studied mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping only.
Publication Title
Combined expression trait correlations and expression quantitative trait locus mapping.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stearoyl-CoA desaturase 1-deficient (SCD1-/-) mice have impaired monounsaturated fatty acid (MUFA) synthesis. When maintained on a very low-fat, high-carbohydrate (VLF-HC) diet, SCD1-/- mice develop severe hypercholesterolemia characterized by an increase in apolipoprotein B-containing lipoproteins and the appearance of lipoprotein-X. Additionally, high-density lipoprotein cholesterol is dramatically reduced in VLF-HC SCD1-/- mice. The concomitant presence of elevated plasma bile acids, bilirubin and aminotransferases in the VLF-HC SCD1-/- mouse are indicative of hepatic dysfunction. Supplementation of the VLF-HC diet with unsaturated fat (canola oil), but not saturated fat (coconut oil), prevents these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing low-density lipoprotein cholesterol, signifying an additional role for dietary polyunsaturated fatty acid deficiency in the development of this phenotype. These results indicate that lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction.
Publication Title
Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Compelling evidence suggests that mitochondrial dysfunction contributes to the pathogenesis of heart failure, including defects in the substrate oxidation, and the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). However, whether such changes occur early in the development of heart failure, and are potentially involved in the pathologic events that lead to cardiac dysfunction is unknown. To address this question, we conducted transcriptomic/metabolomics profiling in hearts of mice with two progressive stages of pressure overload-induced cardiac hypetrophy: i) cardiac hypertrophy with preserved ventricular function achieved via transverse aortic constriction for 4 weeks (TAC) and ii) decompensated cardiac hypertrophy or heart failure (HF) caused by combining 4 wk TAC with a small apical myocardial infarction. Transcriptomic analyses revealed, as shown previously, downregulated expression of genes involved in mitochondrial fatty acid oxidation in both TAC and HF hearts compared to sham-operated control hearts. Surprisingly, however, there were very few changes in expression of genes involved in other mitochondrial energy transduction pathways, ETC, or OXPHOS. Metabolomic analyses demonstrated significant alterations in pathway metabolite levels in HF (but not in TAC), including elevations in acylcarnitines, a subset of amino acids, and the lactate/pyruvate ratio. In contrast, the majority of organic acids were lower than controls. This metabolite profile suggests bottlenecks in the carbon substrate input to the TCA cycle. This transcriptomic/metabolomic profile was markedly different from that of mice PGC-1a/b deficiency in which a global downregulation of genes involved in mitochondrial ETC and OXPHOS was noted. In addition, the transcriptomic/metabolomic signatures of HF differed markedly from that of the exercise-trained mouse heart. We conclude that in contrast to current dogma, alterations in mitochondrial metabolism that occur early in the development of heart failure reflect largely post-transcriptional mechanisms resulting in impedance to substrate flux into the TCA cycle, reflected by alterations in the metabolome.
Publication Title
Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples