Cardiac endothelial cells and cardiomyocytes alter their communication properties in diabetic mice

Abstract Objective We aimed to explore the heterogeneities and communication properties of cardiac CMs and ECs in diabetes. Methods GSE213337 dataset was retrieved from NCBI Gene Expression Omnibus, containing the single-cell RNA sequencing data of hearts from the control and streptozotocin-induced diabetic mice. Cell cluster analysis was performed to identify the cell atlas. Data of CMs and ECs were extracted individually for re-cluster analysis, functional enrichment analysis and trajectory analysis. Cell communication analysis was conducted to explore the altered signals and significant ligand-receptor interactions. Results Eleven cell types were identified in the heart tissue. CMs were re-clustered into four subclusters, and cluster 4 was dominant in diabetic condition and enriched in cellular energy metabolism processes. ECs were re-clustered into six subclusters, and clusters 2, 4 and 5 were dominant in the diabetic condition and mainly enriched in cellular energy metabolism and lipid transport processes. The cellular communication network was altered in the diabetic heart. ECs dominated the overall signaling and notably increased the ANGPTL and SEMA4 signals in the diabetic heart. Four significant ligand-receptor pairs implicating the two signals contributed to the communication between ECs and other cell types, including Angptl1-(Itga1 + Itgb1), Angptl4-Cdh5, Angptl4-Sdc3, and Sema4a-(Nrp + Plxna2). The ligand Angptl4 engaged in ECs-CMs communication in a paracrine manner. Conclusion Single-cell sequencing analysis revealed heterogeneities of ECs and CMs in diabetes, Angptl4-Cdh5 and Angptl4-Sdc3 were involved in the communication between ECs and CMs in diabetes.