Single Nuclei RNA sequencing analysis on Murine model for Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a rare genetic condition marked by the replacement of heart muscle with fibrofatty tissue, primarily in the right ventricle. Gene mutations encoding the proteins that comprise desmosomes, specialized cell junctions that support the preservation of the structural integrity of cardiac muscle cells, are responsible for about 60% of ACM cases. Desmosomes can become weaker due to mutations in the desmosomal genes, which can result in desmosome detachment and the development of fibrofatty tissue in the heart. The most frequently involved genes are those encoding plakophilin-2, desmoplakin and desmoglein-2 (DSG2). Additionally, single nuclei RNA sequencing (snRNA-seq) is a potent method that enables researchers to examine the gene expression patterns of specific cells. In this work, we employed snRNA-seq in a DSG2 transgenic murine model to examine the gene expression profiles of various cardiac cell types, such as cardiomyocytes, fibroblasts, endothelial cells, and fibro-adipogenic precursors. The findings demonstrated the alterations in the expression of genes associated with cardiac development and extracellular matrix (ECM) regulation in mice with ACM when compared to their wild type.