心肌细胞的成熟及其转录调控

Transcriptional Regulation of Cardiomyocyte Maturation

哺乳动物心肌细胞在出生后经历了一系列巨大的转变,由胚胎期的不成熟细胞转变为成熟心肌细胞。这些转变包括细胞形态、细胞周期、代谢模式、电生理等许多方面。心肌细胞的成熟过程决定了成年心肌细胞的状态和功能,包括其微弱的再生能力。在多种先天性心脏病中,这一过程都受到了影响,诱发成年心脏疾病。因此,解析出生后心肌细胞成熟这一发育生物学重要现象的具体转变过程,以及调控这些转变的分子机制,不仅可以鉴定心肌细胞失去增殖能力的机制,也可能加深人们对先天性心脏疾病的理解,从而找到促进心脏再生或者治疗先天性心脏疾病的药物靶点。心肌细胞在出生后的成熟由出生后的多种体内外环境的改变所诱导,经过高度协同的转录程序通过基因表达的改变来实现。随着多种新工具的出现,心肌细胞成熟的分子机制研究正在进入数据和理论层出不穷的崭新时代。该综述回顾了过去几十年里来对心肌细胞成熟多方面表型变化的探索,着重总结了近年来对心肌细胞成熟的转录调控的研究成果,并对未来可能的新发现和新理论进行了探讨。

Immature embryonic cardiomyocytes in mammals undergo a series of transformation after birth to become mature adult cardiomyocytes.The size and shape,cell cycle,metabolism,and electrophysiology of the cardiomyocytes all go through drastic changes during the maturation process,which determines the state and function of adult cardiomyocytes,and especially their limited regenerative capacity.And the maturation process is affected in multiple congenital heart diseases,predisposing the patients to adult heart conditions.Therefore,it is crucial to examine this important process in detail,and dissect the underlying molecular mechanisms,for better understanding the limited proliferative capacity of adult cardiomyocytes,and congenital heart diseases,as well as finding drug targets for treating heart diseases.The maturation process of cardiomyocytes is induced by multiple postnatal stimuli,and is regulated by a highly orchestrated transcriptional program.Currently,the research on the molecular mechanism of this process is entering a new era of massive new data and new theories,thanks to new technologies and new tools available.This review summarizes the explorations in the last few decades on the phenotypic changes during cardiomyocyte maturation,with an emphasis on the transcriptional regulation of the process,and discusses possible future discoveries and theories.