Direct Cardiac Reprogramming in the Omics Era: Advances, Mechanisms, and Applications.

Area of Science:

• Cardiovascular Research
• Regenerative Medicine
• Molecular Biology

Background:

• Cardiovascular disease causes significant mortality, with limited cardiomyocyte regeneration after injury.
• Heart damage leads to scar formation and progressive cardiac dysfunction, often resulting in heart failure.
• Direct cardiac reprogramming offers a novel therapeutic strategy by converting fibroblasts into induced cardiomyocyte-like cells (iCMs).

Purpose of the Study:

• To review omics-based insights into direct cardiac reprogramming.
• To identify mechanisms enabling or hindering fibroblast-to-iCM conversion.
• To discuss future directions for clinical applications of cardiac reprogramming.

Main Methods:

• Single-cell transcriptomics to map gene expression trajectories.
• Epigenomic studies (chromatin accessibility, histone modifications, DNA methylation) to understand cell fate.
• Post-transcriptional and proteomic analyses to reveal RNA processing and protein network dynamics.
• Metabolic studies to investigate metabolite flux in iCM maturation.

Main Results:

• Omics approaches provide a comprehensive framework for understanding fibroblast-to-iCM conversion.
• Detailed insights into gene expression, epigenetic regulation, RNA processing, protein remodeling, and metabolic shifts during reprogramming.
• Identification of barriers and facilitators for efficient iCM generation.

Conclusions:

• Multi-omics data are crucial for advancing direct cardiac reprogramming.
• Understanding these mechanisms is key to improving the efficacy and clinical translation of cell-based cardiac repair.
• Future research should focus on optimizing reprogramming strategies for therapeutic benefit in cardiovascular disease.