Novel insights into post-myocardial infarction cardiac remodeling through algorithmic detection of cell-type composition shifts.

ABSTRACT: Interpreting bulk RNA sequencing from heterogeneous tissues like the post-myocardial infarction (MI) heart is confounded by dynamic changes in cell-type composition. To address this, we developed a computational approach using single-nucleus RNA sequencing (snRNA-seq) references to estimate and correct for cell-type abundance shifts in bulk transcriptomic data. We applied this method to analyze infarct border zone transcriptomes from wild-type (WT) and cardiomyocyte-specific α1A-adrenergic receptor knockout (cmAKO) mice subjected to MI via left coronary artery ligation or sham surgery. Our analysis revealed exaggerated cardiomyocyte loss and fibroblast gain in cmAKO mice post-MI compared to WT, implicating α1A-ARs in maintaining cellular homeostasis. We then demonstrate the confounding eff

SUBMITTER: Gural B 

PROVIDER: S-EPMC12309993 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature