Single-cell RNA sequencing of mouse left ventricle reveals cellular diversity and intercommunication.

Abstract

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10× Genomics). Detailed t-distributed stochastic neighbor embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2, and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits > 2, P < 0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included 5 subtypes, fibroblasts comprising 7 subtypes, and macrophages contained 11 subtypes. The key representative DEGs (P < 0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, and Clec4e and Trem-1 in cluster 3 of macrophages perhaps involved in the occurrence of atherosclerosis, heart failure, and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.