Background and Significance: Myocardial infarction (MI) remains a leading cause of death globally. Despite advancements in acute treatment, the understanding of cardiac remodeling processes post-MI is incomplete, limiting the effectiveness of therapies aimed at reducing late-stage mortality. This study by Kuppe et al, aims to generate a high-resolution, integrative map of human cardiac remodeling post-MI using advanced multi-omic technologies. By profiling multiple physiological zones at distinct time points, the study provides insights into the molecular principles of human myocardial tissue organization, which is crucial for developing novel therapeutic strategies.
Study Subjects and Technology: The study profiled a total of 31 samples from 23 individuals, including four non-transplanted donor hearts as controls. The samples were collected from various zones of the myocardium, including necrotic, ischemic, border, and remote zones. The technologies used for profiling included single-cell gene expression (snRNA-seq), chromatin accessibility (snATAC-seq), and spatial transcriptomics.
Key Findings:
Cardiac Cell-Type Compositions: The study identified and validated disease-specific cardiac cell states of major cell types, analyzing them in their spatial context and evaluating their dependency on other cell types.
Gene-Regulatory Networks: The researchers inferred gene-regulatory networks differentiating these cell states and projected this information onto specific tissue locations, mapping putative regulators controlling gene expression in specific myocardial tissue zones and disease stages.
Spatial Organization: The study characterized the spatial organization of myocardial tissue, identifying major cell-type niches and their roles in tissue remodeling processes.
Molecular Niches: The researchers identified molecular niches associated with inflammatory and fibrotic processes, providing insights into the spatial heterogeneity of gene expression and its impact on cardiac function.
This comprehensive spatial multi-omic map of human myocardial infarction represents an essential reference for the field, paving the way for advanced mechanistic and therapeutic studies of cardiac disease.
Reference: Kuppe et al, Spatial multi-omic map of human myocardial infarction. Nature, volume 608, pages766–777 (2022)