Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands.
Science. 2023 May 19;380(6646):758-764. doi: 10.1126/science.abo6718. Epub 2023 May 18.
Zebrafish hearts can regenerate by replacing damaged tissue with new cardiomyocytes. Although the steps leading up to the proliferation of surviving cardiomyocytes have been extensively studied, little is known about the mechanisms that control proliferation and redifferentiation to a mature state. We found that the cardiac dyad, a structure that regulates calcium handling and excitation-contraction coupling, played a key role in the redifferentiation process. A component of the cardiac dyad called leucine-rich repeat-containing 10 (Lrrc10) acted as a negative regulator of proliferation, prevented cardiomegaly, and induced redifferentiation. We found that its function was conserved in mammalian cardiomyocytes. This study highlights the importance of the underlying mechanisms required for heart regeneration and their application to the generation of fully functional cardiomyocytes.
斑马鱼的心脏可以通过用新的心肌细胞替换受损组织来再生。虽然导致存活的心肌细胞增殖的步骤已经被广泛研究，但控制增殖和重新分化为成熟状态的机制知之甚少。我们发现，调节钙处理和兴奋-收缩偶联的心脏二联体结构在重新分化过程中发挥了关键作用。心脏二联体的一个组成部分称为富含亮氨酸重复序列 10（Lrrc10），它作为增殖的负调节剂，可防止心脏增大，并诱导重新分化。我们发现它的功能在哺乳动物心肌细胞中是保守的。这项研究强调了心脏再生所需的潜在机制的重要性及其在产生完全功能性心肌细胞中的应用。
