Spatial multi-omic map of human myocardial infarction

Abstract Myocardial infarction is a leading cause of mortality. While advances in the acute treatment have been made, the late-stage mortality is still high, driven by an incomplete understanding of cardiac remodeling processes 1,2 . Here we used single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of different physiological zones and timepoints of human myocardial infarction and human control myocardium to generate an integrative high-resolution map of cardiac remodeling. This approach allowed us to increase spatial resolution of cell-type composition and provide spatially resolved insights into the cardiac transcriptome and epigenome with identification of distinct cellular zones of injury, repair and remodeling. We here identified and validated mechanisms of fibroblast to myofibroblast differentiation that drive cardiac fibrosis. Our study provides an integrative molecular map of human myocardial infarction and represents a reference to advance mechanistic and therapeutic studies of cardiac disease.