Single-cell analysis of cardiomyocyte-specific knockout mice provided strong evidence indicating that p53 in cardiomyocytes increases cell-to-cell transcriptional heterogeneity, induces morphological elongation, and drives pathogenic gene programs by disrupting the adaptive hypertrophy modules and activating the heart failure module, thereby elucidating how DNA damage accumulation leads to heart failure33,34. This evidence concerns the gene TP53 and heart failure.