Project description:Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder, characterized by ventricular ar-rhythmias, contractile dysfunctions and fibro-adipose replacement of the myocardium. Cardiac mesenchymal stromal cells (CMSC) participate to disease pathogenesis by differentiating towards adipocytes and myofibroblasts. Some altered pathways in ACM are known, but many are yet to be discovered. In order to define changes in the gene expression profiles between ACM- and HC-CMSC, we performed a high throughput RNA-seq on 6 ACM and 6 HC samples. Out of 15031 expressed genes, 529 resulted differentially expressed. Through enrichment and gene network analyses, we identified differentially regulated pathways, some of which never associated with ACM, including mitochondrial functioning and chromatin organization. Functional validations confirmed that ACM-CMSC exhibited a higher amount of active mitochondria and ROS production, a lower proliferation rate and a more pronounced epicardial-to-mesenchymal transition, compared to controls. In conclusion, ACM-CMSC -omics revealed some additional altered molecular pathways, relevant in the disease pathogenesis, which may constitute novel targets for specific therapies.
Project description:Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder, characterized by ventricular ar-rhythmias, contractile dysfunctions and fibro-adipose replacement of the myocardium. Cardiac mesenchymal stromal cells (CMSC) participate to disease pathogenesis by differentiating towards adipocytes and myofibroblasts. Some altered pathways in ACM are known, but many are yet to be discovered. In order to define changes in the gene expression profiles between ACM- and HC-CMSC, we performed a high throughput Bisulfite-seq on 6 ACM and 6 HC samples. Out of 12466 expressed peaks, 30 resulted differentially expressed. Through enrichment and gene network analyses, we identified differentially regulated pathways, some of which never associated with ACM, including mitochondrial functioning and chromatin organization. Functional validations confirmed that ACM-CMSC exhibited a higher amount of active mitochondria and ROS production, a lower proliferation rate and a more pronounced epicardial-to-mesenchymal transition, compared to controls. In conclusion, ACM-CMSC -omics revealed some additional altered molecular pathways, relevant in the disease pathogenesis, which may constitute novel targets for specific therapies.
Project description:The aim of the study was to identify significant alterations in genes and molecular functional pathways in comparison with normal and ACM tissue, and detect the marker genes to differentiate the different stage astrocytomas Total RNA was isolated from Seventeen tumor tissue of patients, which included two WHO grade I(T1) and five WHO grade II(T2), III(T3) and IV(T4) samples, and four pooled normal tissue samples. The genome-wide expression analysis was first performed by directly comparing the expression profile of highly enriched different grade astrocytomas and pooled normal tissues, we then applied various data-mining methods to process the 15 different grades tumor tissues sample. Paired T-test and Q-cluster method was performed to explore mark genes validated by qRT-PCR. This study utilized a pathway-specific enrichment analysis of the microarray data and quantified the gene expression difference between astrocytomas tumor and pooled normal tissues. BioCarta and KEGG pathways of the ACM compared to normal tissue were identified through enrichment tests on gene lists obtained using SAM, while GO is organized into hierarchical annotations in the context of normal cellular function, the BioCarta and KEGG database organizes the genes(gen products) into pathway reaction maps and functional complexes, including some disease-specific pathway
Project description:The aim of the study was to identify significant alterations in genes and molecular functional pathways in comparison with normal and ACM tissue, and detect the marker genes to differentiate the different stage astrocytomas
Project description:The goal of this experiment is to identify gene ontology pathways and differentially expressed genes that distinguish mature iPSC-aCM, immature iPSC-aCM, and human atrial tissue derived from the same patient.
Project description:Next Generation Sequencing shows that synthetic polyPL and mutSOD1-ACM alter a large and common set of transcripts in primary ventral spinal cord cultures