Single Nucleus RNA sequencing Identifies PLXNA4 Upregulation in End Stage Arrhythmogenic Right Ventricular Cardiomyopathy [RNA-seq]

We carried out single-nucleus RNA sequencing (snRNA-seq) on 11 non-failing and 8 ARVC patient right ventricular samples and transcriptionally profiled 139,347 nuclei. We identified over 4,400 differentially expressed protein coding genes between non-failing and ARVC samples across cell types.

When compared to dilated, hypertrophic and ischemic cardiomyopathy, we found that end stage ARVC is transcriptionally similar to other forms of end stage heart failure. Despite broad transcriptional similarities, we identified seven cardiomyocyte genes and six fibroblast genes that were uniquely dysregulated in ARVC and validated PLXNA4 as a gene with uniquely increased expression in cardiomyocytes in ARVC compared to other cardiomyopathies.