The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: https://twitter.com/@brineshrimp2.
Curr Opin Genet Dev. 2024 Dec;89:102226. doi: 10.1016/j.gde.2024.102226.
Adult mammals are susceptible to substantial cardiomyocyte (CM) loss following various cardiac diseases due to the limited capacity of CM proliferation and regeneration. Recently, direct cardiac reprogramming, converting fibroblasts into induced CMs, has been achieved both in vitro and in vivo through forced expression of transcription factors (TFs). This review encapsulates the advancements made in enhancing reprogramming efficiency and underlying molecular mechanisms. It covers the optimization of TF-based reprogramming cocktails and in vivo delivery platform and recently identified regulators in enhancing reprogramming efficiency. In addition, we discuss recent insights into the molecular mechanisms of direct cardiac reprogramming from single-cell omics analyses. Finally, we briefly touch on remaining challenges and prospective direction of this field.
成年哺乳动物由于心肌细胞(CM)增殖和再生能力有限,在发生各种心脏疾病后易发生大量 CM 丢失。最近,通过强制表达转录因子(TFs),在体外和体内都已经实现了将成纤维细胞直接重编程为诱导型 CM。本综述总结了提高重编程效率的方法和潜在的分子机制。涵盖了基于 TF 的重编程鸡尾酒和体内递送平台的优化,以及最近发现的提高重编程效率的调控因子。此外,我们还讨论了单细胞组学分析在直接心脏重编程分子机制方面的最新进展。最后,我们简要介绍了该领域的剩余挑战和未来方向。