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GSE25700
Mus musculus
30 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Publication Title
Remodeling the cardiac transcriptional landscape with diet.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
NextSeq 500
Description
Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Overall design: Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).
Publication Title
Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Publication Title
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondrial calcium is an important second-messenger controlling fight-or-flight responses in the heart. The molecular identity of MCU (Mitochondrial Calcium Uniporter) was recently discovered allowing us to test this hypothesis in vivo by expressiing a myocardial delimited dominant negative form of MCU.
Publication Title
Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 62 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of the cystic fibrosis gene Cftr in the colon and small intestine of Cftr-deficient murine model. The hypothesis was loss of Cftr altered expression of genes important in intestinal homeostasis and oncogenic signaling pathways. The results identified potential roles of Cftr in up- or down-regulating major gene clusters that belong to groups of immune response, ion channel, intestinal stem cell and other growth regulators. Overall design: The experiments were designed to analyze the role of Cftr-deficiency in tumorigenesis. The goal of this study was to identify genes and pathways associated with Cftr-deficiency in Apc wildtype and ApcMin mice. Total RNAs were isolated from mice, and subjected to deep sequencing, in duplicates, using Illumina HiSeq 2500. Samples that were sequenced in the same batch were analyzed in pair-wise using Tophat-Cuffdiff pipeline as outlined in Nature Protocol from Trapnell C. et al, 2012. The results indicated that Cftr-deficiency overlapped with genes and pathways involved in immune and inflammatory signaling, stem cell regulation, and Wnt/beta catenin signaling. Total RNA was isolated from multiple colon tumors and multiple small intestine tumors from Apc wildtype Cftr-deficient mice, ApcMin Cftr-deficient mice, and ApcMin Cftr wildtype mice. Total RNA was also obtained from Apc wildtype normal colon (epithelial cells) and normal duodenum (whole duodenum minus villi) from three Cftr wildtype and three Cftr-deficient mice. RNA Seq was then conducted on all samples with at least two replicates for each biological sample. Please note that 1) The 23 mice were processed in several batches, and two sequencing runs were carried out at two different dates. Â To control for the batch effect of sequencing, some samples were included in both runs (run1 and run2). 2) To reach the desired sequencing depth and to keep loading balance, each sample was split into halves, and sequenced on two lanes (L007 and L008 for run1, L006 and L007 for run2). therefore, for 11 samples, there are 4 technical replicates, including the 2-batches and 2-lane sequencing method. For the remaining 12 samples, there are 2 technical replicates, referring to the 2-lane sequencing. 3) some of the mice are heterozygous mutant of CFTR gene (CFTRhet), named as "CFTR knockdown".
Publication Title
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the cystic fibrosis gene Cftr in the colon and small intestine of Cftr-deficient murine model. The hypothesis was loss of Cftr altered expression of genes important in intestinal homeostasis and oncogenic signaling pathways. The results identified potential roles of Cftr in up- or down-regulating major gene clusters that belong to groups of immune response, ion channel, intestinal stem cell and other growth regulators.
Publication Title
CFTR is a tumor suppressor gene in murine and human intestinal cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine complementary analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions that demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR// were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.
Publication Title
Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.
Sample Metadata Fields
No sample metadata fields
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