Si Tian-En, Li Zhixiao, Zhang Jingjing, Su Songxue, Liu Yupeng, Chen Shiyue, Peng Guang-Hua, Cao Jing, Zang Weidong
Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou, China.
Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.
Front Cell Dev Biol. 2023 Jun 15;11:1157893. doi: 10.3389/fcell.2023.1157893. eCollection 2023.
Retinal degenerative diseases, characterized by retinal neuronal death and severe vision loss, affect millions of people worldwide. One of the most promising treatment methods for retinal degenerative diseases is to reprogram non-neuronal cells into stem or progenitor cells, which then have the potential to re-differentiate to replace the dead neurons, thereby promoting retinal regeneration. Müller glia are the major glial cell type and play an important regulatory role in retinal metabolism and retinal cell regeneration. Müller glia can serve as a source of neurogenic progenitor cells in organisms with the ability to regenerate the nervous system. Current evidence points toward the reprogramming process of Müller glia, involving changes in the expression of pluripotent factors and other key signaling molecules that may be regulated by epigenetic mechanisms. This review summarizes recent knowledge of epigenetic modifications involved in the reprogramming process of Müller glia and the subsequent changes to gene expression and the outcomes. In living organisms, epigenetic mechanisms mainly include DNA methylation, histone modification, and microRNA-mediated miRNA degradation, all of which play a crucial role in the reprogramming process of Müller glia. The information presented in this review will improve the understanding of the mechanisms underlying the Müller glial reprogramming process and provide a research basis for the development of Müller glial reprogramming therapy for retinal degenerative diseases.
视网膜退行性疾病以视网膜神经元死亡和严重视力丧失为特征，影响着全球数百万人。视网膜退行性疾病最有前景的治疗方法之一是将非神经元细胞重编程为干细胞或祖细胞，这些细胞随后有可能重新分化以替代死亡的神经元，从而促进视网膜再生。穆勒胶质细胞是主要的神经胶质细胞类型，在视网膜代谢和视网膜细胞再生中起重要的调节作用。在具有神经系统再生能力的生物体中，穆勒胶质细胞可作为神经源性祖细胞的来源。目前的证据指向穆勒胶质细胞的重编程过程，涉及多能因子和其他可能受表观遗传机制调控的关键信号分子表达的变化。本综述总结了穆勒胶质细胞重编程过程中涉及的表观遗传修饰的最新知识，以及随后基因表达的变化和结果。在生物体中，表观遗传机制主要包括DNA甲基化、组蛋白修饰和微小RNA介导的miRNA降解，所有这些在穆勒胶质细胞的重编程过程中都起着至关重要的作用。本综述中提供的信息将增进对穆勒胶质细胞重编程过程潜在机制的理解，并为开发用于视网膜退行性疾病的穆勒胶质细胞重编程疗法提供研究基础。
