Spatial transcriptomic profiling of TOP2B-driven anthracycline-induced cardiotoxicity in mouse hearts

Anthracycline-induced cardiotoxicity (AIC) is a major dose-limiting toxicity in cancer patients, traditionally attributed to off-target inhibition of TOP2B in cardiomyocytes. Here, we performed spatial transcriptomic profiling of mouse hearts to investigate the molecular mechanisms underlying AIC and TOP2B-mediated cardiac dysfunction. Using a tamoxifen-inducible, cardiomyocyte-specific human TOP2B transgenic mouse model, we analyzed spatial gene expression changes associated with heart failure phenotypes. Visium spatial RNA sequencing revealed dysregulation of cardiac contractile and metabolic pathways, including MYH6/MYH7 switching, NPPA upregulation, and UCP3 suppression. These data support a model in which TOP2B overexpression disrupts cardiomyocyte homeostasis and contributes directly to heart failure. This dataset provides a spatially resolved transcriptomic resource for studying TOP2B-driven cardiotoxicity and therapeutic intervention strategies.