Single-Cell and Spatial Transcriptomic Profiling of Cardiac Fibroblasts Following Myocardial Infarction
Comprehensive Overview
Published in Scientific Data in 2026, this data descriptor asked what molecular transition governs cardiac fibroblasts as they shift from responding to a heart attack to actively repairing the damaged tissue, and whether a richly annotated, publicly shareable dataset could capture and validate that transition. After inducing myocardial infarction in genetically engineered mice through surgical ligation of a coronary artery, researchers isolated cardiac fibroblasts at multiple time points across the first week of healing and profiled them using bulk RNA sequencing to track known activation and repair genes, single-cell RNA sequencing of nearly 28,000 individual cells sorted into healthy and post-injury groups, spatial transcriptomics mapping gene activity directly onto heart tissue sections, and RNA velocity analysis tracing each cell's transcriptional trajectory over time. They further validated their findings using in situ hybridization and immunofluorescence imaging, then tested whether the same molecular signature appeared in pig hearts after induced infarction and in heart tissue donated by human patients with ischemic cardiomyopathy. The topline result was the identification of a defined three-to-five-day activation window in which fibroblasts commit to a reparative, scar-forming identity, alongside a newly implicated gene marking that transition consistently across all three species.
Outcomes and Implications
The most important finding was the identification of Asporin as a novel candidate marker of the shift from generally activated cardiac fibroblasts to the specialized reparative subtype that orchestrates scar formation and prevents the heart wall from rupturing after infarction. Asporin's expression was spatially concentrated in the gradient running from the border zone into the infarct core between three and seven days post-injury, and it appeared consistently across mouse, pig, and human tissue, suggesting a conserved role rather than a species-specific quirk. Supporting this central finding, the single-cell atlas of nearly 28,000 fibroblasts resolved 17 distinct cellular clusters and revealed two separate transcriptional programs active during healing, only one of which followed a branching trajectory toward the reparative fibroblast state, indicating that this fate is a specific, traceable commitment rather than a uniform default response. Spatial transcriptomic mapping independently confirmed that the reparative gene signature was enriched precisely within the infarcted region. Extending these findings beyond mice, the authors validated the same molecular pattern in porcine hearts tracked out to six months after infarction and in biopsy samples from human ischemic cardiomyopathy patients, using both gene expression and protein-level analysis. The authors conclude that this publicly deposited, multi-modal dataset offers other researchers a well-annotated reference framework for studying how fibroblasts behave during cardiac injury, one they expect will support comparative analyses, benchmarking of new computational methods, and generation of new hypotheses, with potential relevance extending to fibroblast biology and tissue repair in organs beyond the heart.