We carried out bulk RNA sequencing of normal adult mouse CMs (Control-CMs) and adult mouse CMs with ectopic overexpression of Yamanaka factors (Oct4, Sox2, Klf4, Myc, OSKM-CMs), based on a hypothesis that OSKM would induce at least partial CM dedifferentiation in vivo. More than 2,000 genes were differentially expressed between Control- and OSKM-CMs, which were enriched for gene ontology (GO) terms related to multiple key aspects of CM dedifferentiation. This study provides a genome-wide transcriptional profile of dedifferentiating CMs induced by OSKM. Overall design: Bulk RNA sequencing of normal adult mouse CMs (Control-CMs, n = 2) and adult mouse CMs with AAV9-mediated ectopic overexpression of OSKM (OSKM-CMs, n = 3)