Spatial Gene Profiling in the Ischemic Heart

Article, see p 1396 Heart failure is a chronic and progressive condition that involves dysfunction and changes in essentially all major cell types present within this organ. The cardiac fibroblast has been largely overlooked in contributing to the eventual demise of the heart in chronic disease states, although fibrosis and the accumulation of extracellular matrix, which are predominately regulated by the cardiac fibroblast, are clearly part of the sequela.1 Therefore, a better understanding of the cardiac fibroblast and its role in the diseased heart at the molecular and genetic levels will be critical in designing new therapeutic approaches to address the multitiered dysfunction that occurs in the failing or acutely injured heart. The study by Lacraz et al2 in this issue of Circulation utilized a new high-spatial resolution transcriptomics technology called tomo-seq.3,4 This novel technological approach allows for bioinformatics-based mapping of differentially expressed genes from spatially oriented cryosections across the infarcted heart at various time points. The authors identified 3-dimensional and inversely correlated signatures of genes involved in molecular signaling pathways relevant to calcium-handling, cardiomyocyte hypertrophy, and fibrosis in both human …