SnRNA-seq reveals differential functional transcriptional pathway alterations in three mutant types of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure, characterized by ventricular dilation, thinning of the ventricular walls, and systolic dysfunction in either the left or both ventricles, often accompanied by fibrosis. Human cardiac tissue is composed of various cell types, including cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), macrophages, lymphocytes and so on. In DCM patients, these cells frequently undergo functional and phenotypic changes, contributing to contractile dysfunction, inflammation, fibrosis, and cell death, thereby increasing the risk of heart failure. This study focuses on DCM patients with mutations (LMNA, RBM20, and TTN) and analyzes functional changes in subpopulations of four cardiac cell types. The study involves functional annotation of subpopulations within each cell type and explores the association between gene mutations and specific functions and pathways. Additionally, the SCENIC method is employed of a particular cell subpopulation with significant functional importance, aiming to identify key transcriptional regulators in specific cell states. By analyzing the expression levels of ligand-receptor pairs in vCM4, vFB2, EC5.0, T cells, and NK cells across the DCM mutant genotypes, we predicted their signaling pathways and communications. This research provides insights into the molecular mechanisms of DCM and potential therapeutic targets.