The adult human heart has limited regenerative capacity. As such, the massive cardiomyocyte loss due to myocardial infarction leads to scar formation and adverse cardiac remodeling, which ultimately results in chronic heart failure. Direct cardiac reprogramming that converts cardiac fibroblast into functional cardiomyocyte-like cells (also called iCMs) holds great promise for heart regeneration. Cardiac reprogramming has been achieved both in vitro and in vivo by using a variety of cocktails that comprise transcription factors, microRNAs, or small molecules. During the past several years, great progress has been made in improving reprogramming efficiency and understanding the underlying molecular mechanisms. Here, we summarize the direct cardiac reprogramming methods, review the current advances in understanding the molecular mechanisms of cardiac reprogramming, and highlight the novel insights gained from single-cell omics studies. Finally, we discuss the remaining challenges and future directions for the field.

成人心脏的再生能力有限。因此，心肌梗塞导致的大量心肌细胞丢失导致瘢痕形成和不利的心脏重塑，最终导致慢性心力衰竭。将心脏成纤维细胞转化为功能性心肌细胞样细胞（也称为 iCM）的直接心脏重编程对心脏再生具有很大的前景。通过使用包括转录因子、microRNA 或小分子的各种混合物，已经在体外和体内实现了心脏重编程。在过去的几年中，在提高重编程效率和理解潜在的分子机制方面取得了很大进展。在这里，我们总结了直接心脏重编程方法，回顾目前在理解心脏重编程的分子机制方面取得的进展，并强调从单细胞组学研究中获得的新见解。最后，我们讨论了该领域的剩余挑战和未来方向。