Begeman Ian J, Guyer Megan E, Kang Junsu
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Semin Cell Dev Biol. 2025 Jun;170:103610. doi: 10.1016/j.semcdb.2025.103610. Epub 2025 Apr 10.
The adult mammalian heart has limited regenerative capacity. Cardiac injury, such as a myocardial infarction (MI), leads to permanent scarring and impaired heart function. In contrast, neonatal mice and zebrafish possess the ability to repair injured hearts. Cardiac regeneration is driven by profound transcriptional changes, which are controlled by gene regulatory elements, such as tissue regeneration enhancer elements (TREEs). Here, we review recent studies on cardiac injury/regeneration enhancers across species. We further explore regulatory mechanisms governing TREE activities and their associated binding regulators. We also discuss the potential of TREE engineering and how these enhancers can be utilized for heart repair. Decoding the regulatory logic of cardiac regeneration enhancers presents a promising avenue for understanding heart regeneration and advancing therapeutic strategies for heart failure.
成年哺乳动物的心脏再生能力有限。心脏损伤，如心肌梗死（MI），会导致永久性瘢痕形成和心脏功能受损。相比之下，新生小鼠和斑马鱼具有修复受损心脏的能力。心脏再生由深刻的转录变化驱动，这些变化由基因调控元件控制，如组织再生增强子元件（TREEs）。在这里，我们综述了近期关于跨物种心脏损伤/再生增强子的研究。我们进一步探索了控制TREE活性及其相关结合调节因子的调控机制。我们还讨论了TREE工程的潜力以及这些增强子如何用于心脏修复。解码心脏再生增强子的调控逻辑为理解心脏再生和推进心力衰竭治疗策略提供了一条有前景的途径。
