The ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice. Overall design: Whole-transcriptome profiling of the cerebral cortex of wild-type control C57BL/6J mice and two independent Plat-/- mice strains on the C57BL/6J background.
Passenger mutations and aberrant gene expression in congenic tissue plasminogen activator-deficient mouse strains.
Age, Specimen part, Cell line, Subject
View SamplesHuman pluripotent stem cells in culture are often associated with the prime state which represents a more developed state relative to the nave state which is often associated with the inner cell mass and thought to have the potential to give rise to all cell types. We have developed a small molecule-driven cocktail FMM that maintains human pluripotent stem cells in a state similar to the naive state as defined by several properties including gene expression profile.
Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells.
Specimen part
View SamplesValproic acid (VPA) is a short-chain fatty acid used in the treatment of epilepsy and also considered to be an epigenetic modifier by functioning as a histone deacetylase (HDAC)-inhibitor. The aim of this study was to search for gene altered by VPA in human endothelial cells.
Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression.
Specimen part, Treatment
View SamplesWe used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies
Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sex, Specimen part, Treatment
View SamplesTissue macrophages from peritoneal cavity, lung, liver, spleen, small intestine and adipose tissue and M-CSF derived bone marrow derived macrophages (BMDMs) were determined for gene expression.
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sex, Specimen part
View SamplesAnalysis of whole genome expression changes in livers from wild type animals and animals with a liver specific transgenic over expression of Cyp7a1. Mice were given a chronic, repetitive administration of LPS for 7 days. Our prior analysis had indicated that inflammation suppresses Cyp7a1 and that this leads to accumulation of intermediates in the mevalonate biosynthesis pathway. Here, we hypothesized that over expression of Cyp7a1 would not affect the changes in transcriptional state due to chronic administration of LPS. We provide gene expression data which evaluates this question. Here we find that over expression of Cyp7a1 minimally alters the transcriptome of livers in an untreated state, and that it has small effects on the response to chronic LPS. Overall design: Total RNA isolated from livers of wild type and liver specific Cyp7a1 transgenic animals treated with or without recurrent, daily LPS injections (1.5mg/kg) for 7 days. There are two biological replicates per condition. Samples are a matrix of all conditions reported as FPKMs.
The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia.
Sex, Specimen part, Cell line, Subject
View SamplesBMDMs were stimulated with ATRA and/or omentum culture supernatant and gene expression was determined by Illumina microarray
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Specimen part, Treatment
View SamplesAnalysis of whole genome expression changes in primary hepatocytes in response to chronic stimulation with inflammatory cytokines. We hypothesized that chronic treatment of primary hepatocytes with TNF would result in a reprogramming of the cell's transcriptome to improve adaptation to the presence of a chronic inflammatory stress. Here we provide expression analysis detailing genes upregulated, downregulated, and unchanged after 2 days of TNF treatment. We have included gene expression profiling of cells treated with TNF for 2 hours to help isolate the changes unique to chronic TNF treatment of primary hepatocytes.
The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia.
Sex, Specimen part
View SamplesIn this study, we have identified MEF2A-sensitive genes in atrial and ventricular chambers of the adult heart. MEF2A is a member of the myocyte enhancer factor 2 (MEF2) family of transcription factors. MEF2 proteins are expressed in skeletal and cardiac muscle tissues and are conserved across many mammalian species, but the gene programs regulated by MEF2A in adult cardiac chambers are largely unknown. We compared gene expression profiles between WT and Mef2a knockout atria and ventricles from adult mice, and the results identified distinct and overlapping sets of genes sensitive to the loss of MEF2A in the adult heart.
The transcription factor MEF2A fine-tunes gene expression in the atrial and ventricular chambers of the adult heart.
Specimen part
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