Transcriptome and epigenome profiling of regenerative versus nonregenerative mouse hearts following myocardial infarction identified Ccl24 and Igf2bp3 as regulators of cardiomyocyte proliferation.
The identification of Ccl24 and Igf2bp3 provides novel insights into the molecular basis of neonatal heart regeneration and highlights potential targets for promoting cardiac regeneration.
The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and nonregenerative mouse hearts over a 7-d time period following myocardial infarction injury. By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration, and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and a retained embryonic cardiogenic gene program that is active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that can be modulated to promote heart regeneration.
Wang et al. (Mon,) conducted a other in Myocardial infarction. Regenerative mouse hearts vs. Nonregenerative mouse hearts was evaluated on Transcriptional programs and regulators of cardiomyocyte proliferation. Transcriptome and epigenome profiling of regenerative versus nonregenerative mouse hearts following myocardial infarction identified Ccl24 and Igf2bp3 as regulators of cardiomyocyte proliferation.