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What we know about cardiomyocyte dedifferentiation
Journal of Molecular and Cellular Cardiology ( IF 4.9 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.yjmcc.2020.11.016
Yike Zhu 1 , Vinh Dang Do 1 , A Mark Richards 2 , Roger Foo 1
Affiliation  

Cardiomyocytes (CMs) lost during cardiac injury and heart failure (HF) cannot be replaced due to their limited proliferative capacity. Regenerating the failing heart by promoting CM cell-cycle re-entry is an ambitious solution, currently vigorously pursued. Some genes have been proven to promote endogenous CM proliferation, believed to be preceded by CM dedifferentiation, wherein terminally differentiated CMs are initially reversed back to the less mature state which precedes cell division. However, very little else is known about CM dedifferentiation which remains poorly defined. We lack robust molecular markers and proper understanding of the mechanisms driving dedifferentiation. Even the term dedifferentiation is debated because there is no objective evidence of pluripotency, and could rather reflect CM plasticity instead. Nonetheless, the significance of CM transition states on cardiac function, and whether they necessarily lead to CM proliferation, remains unclear. This review summarises the current state of knowledge of both natural and experimentally induced CM dedifferentiation in non-mammalian vertebrates (primarily the zebrafish) and mammals, as well as the phenotypes and molecular mechanisms involved. The significance and potential challenges of studying CM dedifferentiation are also discussed. In summary, CM dedifferentiation, essential for CM plasticity, may have an important role in heart regeneration, thereby contributing to the prevention and treatment of heart disease. More attention is needed in this field to overcome the technical limitations and knowledge gaps.



中文翻译:

我们对心肌细胞去分化的了解

在心脏损伤和心力衰竭 (HF) 期间丢失的心肌细胞 (CM) 由于增殖能力有限而无法替代。通过促进 CM 细胞周期重新进入来再生衰竭的心脏是一个雄心勃勃的解决方案,目前正在大力追求。一些基因已被证明可促进内源性 CM 增殖,据信是在 CM 去分化之前发生的,其中终末分化的 CM 最初被逆转回细胞分裂之前的不太成熟的状态。然而,关于 CM 去分化的其他信息知之甚少,这仍然定义不明确。我们缺乏强大的分子标记和对驱动去分化机制的正确理解。甚至术语去分化也存在争议,因为没有多能性的客观证据,而是可以反映 CM 可塑性。尽管如此,CM 过渡态对心脏功能的重要性,以及它们是否必然导致 CM 增殖,仍不清楚。本综述总结了非哺乳动物脊椎动物(主要是斑马鱼)和哺乳动物中自然和实验诱导的 CM 去分化的当前知识状态,以及所涉及的表型和分子机制。还讨论了研究 CM 去分化的意义和潜在挑战。总之,CM去分化对于CM可塑性至关重要,可能在心脏再生中起重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。以及它们是否必然导致 CM 增殖,仍不清楚。本综述总结了非哺乳动物脊椎动物(主要是斑马鱼)和哺乳动物中自然和实验诱导的 CM 去分化的当前知识状态,以及所涉及的表型和分子机制。还讨论了研究 CM 去分化的意义和潜在挑战。总之,CM去分化对于CM可塑性至关重要,可能在心脏再生中起重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。以及它们是否必然导致 CM 增殖,仍不清楚。本综述总结了非哺乳动物脊椎动物(主要是斑马鱼)和哺乳动物中自然和实验诱导的 CM 去分化的当前知识状态,以及所涉及的表型和分子机制。还讨论了研究 CM 去分化的意义和潜在挑战。总之,CM去分化对于CM可塑性至关重要,可能在心脏再生中起重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。本综述总结了非哺乳动物脊椎动物(主要是斑马鱼)和哺乳动物中自然和实验诱导的 CM 去分化的当前知识状态,以及所涉及的表型和分子机制。还讨论了研究 CM 去分化的意义和潜在挑战。总之,CM去分化对于CM可塑性至关重要,可能在心脏再生中起重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。本综述总结了非哺乳动物脊椎动物(主要是斑马鱼)和哺乳动物中自然和实验诱导的 CM 去分化的当前知识状态,以及所涉及的表型和分子机制。还讨论了研究 CM 去分化的意义和潜在挑战。总之,CM去分化对于CM可塑性至关重要,可能在心脏再生中起重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。CM 可塑性必不可少,可能在心脏再生中具有重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。CM 可塑性必不可少,可能在心脏再生中具有重要作用,从而有助于预防和治疗心脏病。该领域需要更多关注以克服技术限制和知识差距。

更新日期:2020-12-16
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