Direct cardiac reprogramming: Toward the era of multi-omics analysis

Limited regenerative capacity of adult cardiomyocytes precludes heart repair and regeneration after cardiac injury. Direct cardiac reprograming that converts scar-forming cardiac fibroblasts (CFs) into functional induced-cardiomyocytes (iCMs) offers promising potential to restore heart structure and heart function. Significant advances have been achieved in iCM reprogramming using genetic and epigenetic regulators, small molecules, and delivery strategies. Recent researches on the heterogeneity and reprogramming trajectories elucidated novel mechanisms of iCM reprogramming at single cell level. Here, we review recent progress in iCM reprogramming with a focus on multi-omics (transcriptomic, epigenomic and proteomic) researches to investigate the cellular and molecular machinery governing cell fate conversion. We also highlight the future potential using multi-omics approaches to dissect iCMs conversion for clinal applications.