Uncovering the heterogeneity and cell fate decisions of endothelial cells after myocardial infarction by single‐cell sequencing

Abstract Background The plasticity of endothelial cells (ECs) is crucial for tissue response to injury. Myocardial infarction can profoundly affect EC function, leading to a shift toward mesenchymal differentiation. Methods We utilized human single‐nucleus RNA sequencing data to investigate the dynamic changes and cellular interactions between normal and post‐infarction ECs. Results We identified two distinct subpopulations of ECs: A transient subpopulation characterized by short‐term mesenchymal gene expression and a long‐term subpopulation characterized by myocardial gene expression. Trajectory analysis revealed the differentiation pathways and potential roles over time and space. Furthermore, we uncovered the proliferation, differentiation, hypoxic, and inflammatory responses of ECs to injury. Conclusions Our study provides a comprehensive and detailed characterization of endothelial cell states, highlighting the role of activated endothelial cell subpopulations in promoting inflammation and tissue repair after infarction.