Project description:Deletion of the melanocortin-4 receptor in mice causes dilated cardiomyopathy that is independent of obesity. Overall design: RNA from left ventricular tissue of MC4R-/- and WT was characterized using RNA-seq
Project description:A novel ppp1r13l sequence variation causes dilated cardiomyopathy and cardiac inflammation. This experiment explores the transcriptome of wa3 mice hearts which are carry deletion and insertion mutations in exon 12 of the Ppp1r13l gene that generate premature stop codon, and exhibit dilated cardio myopathy in a similar manner to a novel human mutation that was recently dicovered.
Project description:miRNA expression in early stage mouse model of dilated cardiomyopathy Apoptosis is a hallmark of multiple etiologies of heart failure, including dilated cardiomyopathy. Since microRNAs are master regulators of cardiac development and key effectors of intracellular signaling, they represent novel candidates for understanding the mechanisms driving the increased dysfunction and loss of cardiomyocytes during cardiovascular disease progression. To determine the role of cardiac miRNAs in the apoptotic response, we used microarray technology to monitor miRNA levels in a validated murine phospholambam mutant model of dilated cardiomyopathy. 24 miRNAs were found significantly differentially expressed, most of which have not been linked to cardiac disease before. We showed that individual silencing of 6 out of 7 significantly down-regulated miRNAs (mir-1, -29c, -30d, -149, -486, -499) led to a strong apoptotic phenotype in cell culture , suggesting they repress pro-apoptotic factors. To identify putative miRNA targets most likely relevant to cell death, we computationally integrated transcriptomic, proteomic and functional annotation data. We showed the dependency of prioritized target abundance on miRNA expression using RNA interference and quantitative mass spectrometry. We concluded that down regulation of key pro-survival miRNAs causes up-regulation of apoptotic signaling effectors that contribute to cardiac cell loss, potentially leading to system decompensation and heart failure. Overall design: Two different microarray platforms, were used to identify and quantify miRNA expression at early stage dilated cardiomyopathy times. Total RNA was collected from mouse ventricle tissues in a transgenic model expressing a mutant form of phospholamban which results in dilated cardiomyopathway versus healthly littermates as a control.
Project description:A novel ppp1r13l sequence variation causes dilated cardiomyopathy and cardiac inflammation. In this experiment we knocked down IASPP (protein product of ppp1r13l) in cardiomyocytes and exposed them to lipopolysaccharide for time interval of 2 and 4 hours. Transcriptome was examined using rna-seq high-throughput sequencing.
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice. Overall design: Examination of transcription of Mouse PGCs
Project description:We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist . Stromal vascular fractions (SVF) from mice (n = 3/group) that received vehicle or beta3 adrenergic receptor agonist, CL, treatment were served for RNA extraction and hybridization on Affymetrix microarrays. We are trying to find out angiogenic factors genes dynamics during white adipose tissues (WAT) - beige transition.
Project description:Gene expression in the right ventricle is different in control patients as compared to either idiopathic dilated cardiomyopathy or pulmonary arterial hypertension Two human hearts obtained at autopsy from each of control, pulmonary hypertension, and dilated cardiomyopathy