A human cell atlas of the pressure-induced hypertrophic heart

Abstract Pathological cardiac hypertrophy is a leading cause of heart failure, but knowledge the full repertoire cells and their gene expression profiles in human hypertrophic missing. Here, by using large-scale single-nucleus transcriptomics, we present transcriptional response cardiomyocytes to pressure overload caused aortic valve stenosis describe major alterations cellular crosstalk. Hypertrophied had reduced input from endothelial fibroblasts. Genes encoding Eph receptor tyrosine kinases, particularly EPHB1 , were significantly downregulated hypertrophied heart. Consequently, activation its ligand ephrin (EFN)B2, which mainly expressed cells, was reduced. EFNB2 inhibited cardiomyocyte vitro, while silencing induced co-cultured cardiomyocytes. Our cell atlas highlights importance intercellular crosstalk disease pathogenesis provides valuable resource.