The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in human cardiac stromal cells
Johannes Rainer1, Viviana Meraviglia2, Hagen Blankenburg3
1Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Viale Druso 1, 39100, Bolzano, Italy. johannes.rainer@eurac.edu.
Insights
Researchers identified specific gene and microRNA (miRNA) expression profiles in cardiac stromal cells (CStCs) from arrhythmogenic cardiomyopathy (ACM) patients. These findings highlight potential roles for cell adhesion and specific miRNAs in ACM pathogenesis.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Cell Biology
Background:
- Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder affecting heart muscle.
- Pathogenesis involves abnormal cell adhesion, cardiomyocyte death, and fibrosis.
- Cardiac stromal cells (CStCs) are newly recognized contributors to ACM.
Purpose of the Study:
- To identify unique gene and microRNA (miRNA) expression profiles in CStCs from ACM patients.
- To understand the role of CStCs in the molecular mechanisms of ACM.
Main Methods:
- Human CStCs were isolated from endomyocardial biopsies of ACM patients and healthy controls.
- miRNA expression profiling was performed using TaqMan Low Density Arrays.
- Gene expression quantification utilized high-throughput sequencing.
Main Results:
- Identified 3 significantly differentially expressed miRNAs and 272 genes in ACM CStCs.
- Differentially expressed genes and miRNA targets are enriched in cell adhesion pathways.
- Network analyses revealed clusters related to cell adhesion, extracellular matrix, lipid transport, and ephrin signaling.
Conclusions:
- First characterization of the coding and non-coding transcriptome of ACM CStCs.
- Evidence suggests a role for miRNAs, particularly miR-29b-3p, in ACM pathogenesis.
- Findings provide insights into CStC contribution to ACM disease mechanisms.
Background:
Arrhythmogenic cardiomyopathy (ACM) is a genetic autosomal disease characterized by abnormal cell-cell adhesion, cardiomyocyte death, progressive fibro-adipose replacement of the myocardium, arrhythmias and sudden death. Several different cell types contribute to the pathogenesis of ACM, including, as recently described, cardiac stromal cells (CStCs). In the present study, we aim to identify ACM-specific expression profiles of human CStCs derived from endomyocardial biopsies of ACM patients and healthy individuals employing TaqMan Low Density Arrays for miRNA expression profiling, and high throughput sequencing for gene expression quantification.
Results:
We identified 3 miRNAs and 272 genes as significantly differentially expressed at a 5% false discovery rate. Both the differentially expressed genes as well as the target genes of the ACM-specific miRNAs were found to be enriched in cell adhesion-related biological processes. Functional similarity and protein interaction-based network analyses performed on the identified deregulated genes, miRNA targets and known ACM-causative genes revealed clusters of highly related genes involved in cell adhesion, extracellular matrix organization, lipid transport and ephrin receptor signaling.
Conclusions:
We determined for the first time the coding and non-coding transcriptome characteristic of ACM cardiac stromal cells, finding evidence for a potential contribution of miRNAs, specifically miR-29b-3p, to ACM pathogenesis or phenotype maintenance.
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