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心肌细胞成熟过程中的代谢动力学和表观遗传学调控。

Dynamics of metabolism and regulation of epigenetics during cardiomyocytes maturation.

机构信息

Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, China.

出版信息

Cell Biol Int. 2023 Jan;47(1):30-40. doi: 10.1002/cbin.11931. Epub 2022 Oct 8.

Abstract

Maturation is the last step of heart growth that prepares the organ over the lifetime of the mammal for powerful, effective, and sustained pumping. Structural, gene expression, physiological, and functional specialties of cardiomyocytes describe this mechanism as the heart transits from fetus to adult phases. The main cornerstones of maturation of cardiomyocytes are reviewed and primary regulatory mechanisms are summarized to facilitate and organize these cellular activities. During embryonic development, cardiomyocytes proliferate rigorously but leave the cell cycle permanently immediately after the parturition of the child and experience terminal differentiation. The activation of a host of genes specific for the mature heart is correlated with the exit from the cell cycle. Even when exposed to mitogenic stimuli, the bulk of mature cardiomyocytes do not re-join the cell cycle. The reason for this permanent exit from the cell cycle is shown to be linked with stable switching off of the genes of the cell cycle directly involved in the G2/M transition phase and cytokinesis development. Researchers also trying to explain the molecular mechanism involved in stable inhibition of the gene and described structural changes (epigenetic and chromatin) in this mechanism. Substantial developments in the future with advances in the scientific platforms used for cardiomyocyte maturation research will broaden our understanding of this mechanism and result in better maturation of cardiomyocyte-derived pluripotent stem cells and effective treatment approaches for cardiovascular diseases.

摘要

成熟是心脏生长的最后一步,它使器官在哺乳动物的一生中为强大、有效和持续的泵血做好准备。结构、基因表达、生理和功能方面的特点描述了这一机制,即心脏从胎儿期过渡到成人期。本文综述了心肌细胞成熟的主要基石,并总结了主要的调节机制,以促进和组织这些细胞活动。在胚胎发育过程中,心肌细胞严格增殖,但在孩子出生后立即永久性地离开细胞周期,并经历终末分化。许多特定于成熟心脏的基因的激活与细胞周期的退出相关。即使暴露于有丝分裂刺激下,大部分成熟的心肌细胞也不会重新进入细胞周期。这种永久性的细胞周期退出的原因与直接参与 G2/M 转换阶段和胞质分裂发育的细胞周期基因的稳定关闭有关。研究人员还试图解释涉及基因稳定抑制的分子机制,并描述了该机制中的结构变化(表观遗传和染色质)。随着用于心肌细胞成熟研究的科学平台的进步,未来的研究将大大扩展我们对这一机制的理解,并促进心肌细胞衍生的多能干细胞的更好成熟和心血管疾病的有效治疗方法。

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