Cardiomyopathy in type 1 diabetic patients is characterized by early onset diastolic and late onset systolic dysfunction. The mechanism underlying development of diastolic and systolic dysfunction in diabetes remains unknown.
Activation of a novel long-chain free fatty acid generation and export system in mitochondria of diabetic rat hearts.
Age
View SamplesAblation of the mouse gene for Onecut-2 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here, we examine postnatal development of these Onecut-2 knockout mice, especially the critical period prior to weaning. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in the Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression.
Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine.
Sex, Specimen part
View SamplesCardiac hypertrophy is regulated by the zinc finger-containing DNA binding factors Gata4 and Gata6, both of which are required to mount a productive growth response of the adult heart. To determine if Gata4 and Gata6 are redundant or have non-overlapping roles, we performed cardiomyocyte-specific conditional gene deletions for Gata4 and Gata6 in conjunction with reciprocal replacement with a transgene encoding either Gata4 or Gata6, during the pressure overload response. We determined that Gata4 and Gata6 play a redundant and dosage-sensitive role in programming the hypertrophic growth response itself following pressure overload stimulation. However, non-redundant functions were identified as functional decompensation induced by either Gata4 or Gata6 deletion was not rescued by the reciprocal transgene, and only Gata4 heart-specific deletion produced a reduction in capillary density after pressure overload. Gene expression profiling from hearts of these gene-deleted mice showed both overlapping and unique transcriptional codes, with Gata4 exhibiting the strongest impact. These results indicate that Gata4 and Gata6 play a dosage-dependent and semi-redundant role in programming cardiac hypertrophy, but that each has a unique role in maintaining cardiac homeostasis and adaptation to injury that cannot be compensated by the other.
Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.
Age, Specimen part
View SamplesIn order to identify targets for HDAC4, NRVM were infected with adenoviral vectors encoding beta-Galactosidase or Flag- HDAC4, and incubated in serum free or 10% fetal calf serum containing growth medium for 48 hrs.
Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins.
Specimen part
View SamplesThe beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics.
Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs.
No sample metadata fields
View SamplesThe growth in popularity of RNA expression microarrays has been accompanied by concerns about the reliability of the data especially when comparing between different platforms. Here we present an evaluation of the reproducibility of microarray results using two platforms, Affymetrix GeneChips and Illumina BeadArrays. The study design is based on a dilution series of two human tissues (blood and placenta), tested in duplicate on each platform. By a variety of measures the two platforms yielded data of similar quality and properties. The results of a comparison between the platforms indicate very high agreement, particularly for genes which are predicted to be differentially expressed between the two tissues. Agreement was strongly correlated with the level of expression of a gene. Concordance was also improved when probes on the two platforms could be identified as being likely to target the same set of transcripts of a given gene. These results shed light on the causes or failures of agreement across microarray platforms. The set of probes we found to be most highly reproducible can be used by others to help increase confidence in analyses of other data sets using these platforms.
Experimental comparison and cross-validation of the Affymetrix and Illumina gene expression analysis platforms.
No sample metadata fields
View SamplesSerine 105 phosphorylation of GATA4 is necessary for stress-induced cardiac hypertrophy in vivo.
Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo.
Age, Specimen part
View SamplesE12.5 AV cushion and E17.5 AV valve from wild-type FVB/N mice and in vitro cultured MC3T3 cells
Shared gene expression profiles in developing heart valves and osteoblast progenitor cells.
No sample metadata fields
View SamplesPurpose: The purpose of this study is to compare the transcriptome expression profiles of E13.5 Foxf2-/-;Osr2RFP/+ and control palatal mesenchyme by using RNA-seq analysis. Methods: Foxf2+/- female mice were crossed with Foxf2+/-;Osr2RFP/+ male mice.The embryos were harvested at E13.5. The pair of palatal shelves were dissected from each Osr2-RFP+ embryo. The RFP+ palatal mesenchyme cells were isolated by using fluorescence-activated cell sorting (FACS). RNA-seq analysis was carried out using the FACS-isolated palatal mesenchyme from Foxf2-/-;Osr2RFP/+, Foxf2+/-;Osr2RFP/+ and Osr2RFP/+embryos, respectively. Overall design: The transcriptome expression profiles of E13.5 control and Foxf2-/-Osr2RFP/+ palatal mesenchyme by using RNA-seq analysis, in duplicates, using Illumina HisEq 2000.
A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.
No sample metadata fields
View SamplesKeloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes.
Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology.
Sex, Age, Specimen part, Race
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