Kay Maryam, Soltani Bahram M
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 111-14115, Iran.
Noncoding RNA. 2021 Mar 10;7(1):20. doi: 10.3390/ncrna7010020.
Cardiomyocyte (CM) maturation, which is characterized by structural, functional, and metabolic specializations, is the last phase of CM development that prepares the cells for efficient and forceful contraction throughout life. Over the past decades, CM maturation has gained increased attention due to the fact that pluripotent stem cell-derived CMs are structurally, transcriptionally, and functionally immature and embryonic-like, which causes a defect in cell replacement therapy. The current challenge is to discover and understand the molecular mechanisms, which control the CM maturation process. Currently, emerging shreds of evidence emphasize the role of long noncoding RNAs (lncRNAs) in regulating different aspects of CM maturation, including myofibril maturation, electrophysiology, and Ca handling maturation, metabolic maturation and proliferation to hypertrophy transition. Here, we describe the structural and functional characteristics of mature CMs. Furthermore, this review highlights the lncRNAs as crucial regulators of different aspects in CM maturation, which have the potential to be used for mature CM production. With the current advances in oligonucleotide delivery; lncRNAs may serve as putative therapeutic targets to produce highly mature CMs for research and regenerative medicine.
心肌细胞(CM)成熟以结构、功能和代谢特化为特征,是CM发育的最后阶段,此阶段使细胞为终身高效有力的收缩做好准备。在过去几十年中,由于多能干细胞衍生的CM在结构、转录和功能上不成熟且类似胚胎细胞,这导致细胞替代疗法存在缺陷,因此CM成熟受到了越来越多的关注。当前的挑战是发现并理解控制CM成熟过程的分子机制。目前,新出现的证据强调了长链非编码RNA(lncRNA)在调节CM成熟的不同方面所起的作用,包括肌原纤维成熟、电生理学、钙处理成熟、代谢成熟以及增殖向肥大的转变。在此,我们描述了成熟CM的结构和功能特征。此外,本综述强调lncRNA作为CM成熟不同方面的关键调节因子,具有用于生产成熟CM的潜力。随着目前寡核苷酸递送技术的进步,lncRNA可能作为假定的治疗靶点,用于生产高度成熟的CM以用于研究和再生医学。