Spatial multi-omic map of human myocardial infarction

Myocardial infarction is a leading cause of mortality worldwide 1 . While advances have been made
in acute treatment, an incomplete understanding of remodelling processes has limited the
effectiveness of therapies to reduce late-stage mortality 2 . Here, we generate an integrative high-
resolution map of human cardiac remodelling after myocardial infarction using single-cell gene
expression, chromatin accessibility, and spatial transcriptomic profiling of multiple physiological
zones at distinct time points in myocardium from myocardial infarction and control patients.
Multimodal data integration allowed us to evaluate cardiac cell-type compositions at increased
resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the
identification of distinct tissue structures of injury, repair and remodelling. We identified and
validated disease-specific cardiac cell-states of major cell-types and analysed them in their spatial
context, evaluating their dependency on other cell-types. Our data elucidates molecular principles
of human myocardial tissue organisation, recapitulating a gradual cardiomyocyte and myeloid
continuum following ischemic injury. In total, our study provides an integrative molecular map of
human myocardial infarction and represents an essential reference for the field and paves the way
for advanced mechanistic and therapeutic studies of cardiac disease.EGA study EGAS00001006330