Single-cell RNA-seq of heart reveals intercellular communication drivers of myocardial fibrosis in diabetic cardiomyopathy

• DOI: 10.7554/elife.80479
• Publication Date: 2023-04-03T12:02:11Z
• Authors: Wei Li; Xinqi Lou; Yingjie Zha; Yinyin Qin; Jun Zha; Lei Hong; Zhanli Xie; Shudi Yang; Chen Wang; Jianzhong An; Zhenhao Zhang; Shigang Qiao
• Keywords: Diabetic Cardiomyopathy; Cardiac Fibrosis; Myocardial fibrosis; PDGFRA; Endomyocardial fibrosis

Myocardial fibrosis is the characteristic pathology of diabetes-induced cardiomyopathy. Therefore, an in-depth study cardiac heterogeneity and cell-to-cell interactions can help elucidate pathogenesis diabetic myocardial identify treatment targets for this disease. In study, we investigated intercellular communication drivers in mouse heart with high-fat-diet/streptozotocin-induced diabetes at single-cell resolution. Intercellular protein–protein interaction networks fibroblasts macrophages, endothelial cells, as well epicardial cells revealed critical changes ligand–receptor such Pdgf(s)–Pdgfra Efemp1–Egfr, which promote development a profibrotic microenvironment during progression confirmed that specific inhibition Pdgfra axis could significantly improve fibrosis. We also identified phenotypically distinct Hrc hi Postn fibroblast subpopulations associated pathological extracellular matrix remodeling, were found to be most profibrogenic under conditions. Finally, validated role Itgb1 hub gene-mediated fibroblasts, results through AAV9-mediated knockdown mice. summary, cell mapping provides novel insights into involved remodeling