Peng William G, Getachew Anteneh, Zhou Yang
Department of Biomedical Engineering, Heersink School of Medicine, School of Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, United States.
Stem Cells. 2025 Mar 10;43(3). doi: 10.1093/stmcls/sxaf002.
Heart disease, particularly resulting from myocardial infarction (MI), continues to be a leading cause of mortality, largely due to the limited regenerative capacity of the human heart. Current therapeutic approaches seek to generate new cardiomyocytes from alternative sources. Direct cardiac reprogramming, which converts fibroblasts into induced cardiomyocytes (iCMs), offers a promising alternative by enabling in situ cardiac regeneration and minimizing tumorigenesis concerns. Here we review recent advancements in the understanding of transcriptional and epigenetic mechanisms underlying cardiac reprogramming, with a focus on key early-stage molecular events, including epigenetic barriers and regulatory mechanisms that facilitate reprogramming. Despite substantial progress, human cardiac fibroblast reprogramming and iCM maturation remain areas for further exploration. We also discuss the combinatorial roles of reprogramming factors in governing transcriptional and epigenetic changes. This review consolidates current knowledge and proposes future directions for promoting the translational potential of cardiac reprogramming techniques.
心脏病，尤其是由心肌梗死（MI）导致的心脏病，仍然是主要的死亡原因，这在很大程度上是由于人类心脏的再生能力有限。目前的治疗方法试图从其他来源产生新的心肌细胞。直接心脏重编程可将成纤维细胞转化为诱导性心肌细胞（iCMs），通过实现原位心脏再生并将肿瘤发生风险降至最低，提供了一种很有前景的替代方法。在此，我们综述了对心脏重编程背后的转录和表观遗传机制理解的最新进展，重点关注关键的早期分子事件，包括表观遗传障碍和促进重编程的调控机制。尽管取得了重大进展，但人类心脏成纤维细胞重编程和iCM成熟仍有待进一步探索。我们还讨论了重编程因子在调控转录和表观遗传变化中的组合作用。本综述整合了当前的知识，并为推动心脏重编程技术的转化潜力提出了未来方向。
