(A) Clinical timeline and patient demographics for pediatric anthracycline-induced cardiomyopathy (pAICM) samples, with senescence gene sets used for analyses. (B) Batch-corrected UMAP of nuclei from pAICM, pediatric dilated cardiomyopathy (pDCM), and pediatric donor (pDonor) hearts. (C) Major cardiac cell populations identified by unsupervised clustering and canonical markers. (D) KEGG pathway analysis of pAICM cardiomyocyte-specific genes showing enrichment of cellular senescence pathway. (E) Senescence signature scores across major cardiac cell types, demonstrating increased senescence signature in pAICM samples compared with pDCM and pDonor samples. (Wilcoxon’s rank-sum test with Benjamini-Hochberg FDR correction; ****P < 0.0001). (F) Mean cardiomyocyte expression of representative senescence-associated genes. (G) Representative immunofluorescence staining of pAICM and pDonor myocardium for p21 (green), wheat germ agglutinin (WGA; white), and DAPI (blue). Arrowheads indicate p21⁺ nuclei. Scale bar: 25 μm. (H) Quantification of p21⁺ cardiomyocytes in pAICM and pDonor hearts, aggregated across 2 independent fields of view per individual and 2 patients per disease group. Bars represent disease groups; the bracket indicates the comparison between pAICM and pDonor. Counts above each bar denote p21⁺ cardiomyocytes out of total cardiomyocytes. (Fisher’s exact test on pooled cardiomyocyte counts; ***P < 0.001). LV, left ventricle; UMAP, Uniform Manifold Approximation and Projection; CM, cardiomyocytes; EC, endothelial cells; FB, fibroblasts; PC, pericytes; Mye, myeloid cells; SMC, smooth muscle cells; Lym, lymphoid cells; EndoC, endocardial cells; Neuro, neuronal cells; LEC, lymphatic endothelial cells; Adipo, adipocytes; KEGG, Kyoto Encyclopedia of Genes and Genomes.