Department of Pathology and Laboratory Medicine, McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pathology and Laboratory Medicine, McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
Semin Cell Dev Biol. 2022 Feb;122:37-43. doi: 10.1016/j.semcdb.2021.07.010. Epub 2021 Jul 23.
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，心肌梗死导致大量心肌细胞死亡会导致疤痕形成和心脏不良重构，最终导致慢性心力衰竭。直接将心脏成纤维细胞重编程为功能性心肌样细胞（也称为 iCMs）为心脏再生带来了巨大的希望。通过使用多种转录因子、microRNAs 或小分子组成的鸡尾酒，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分子机制方面取得了巨大进展。在这里，我们总结了直接心脏重编程的方法，回顾了目前对心脏重编程分子机制的理解进展，并强调了单细胞组学研究获得的新见解。最后，我们讨论了该领域面临的剩余挑战和未来方向。
