Berry Kalen, Wang Jiajia, Lu Q Richard
Department of Pediatrics, Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
F1000Res. 2020 Feb 11;9. doi: 10.12688/f1000research.20904.1. eCollection 2020.
Oligodendrocytes are the critical cell types giving rise to the myelin nerve sheath enabling efficient nerve transmission in the central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are maintained throughout life. Deficits in the generation, proliferation, or differentiation of these cells or their maintenance have been linked to neurological disorders ranging from developmental disorders to neurodegenerative diseases and limit repair after CNS injury. Understanding the regulation of these processes is critical for achieving proper myelination during development, preventing disease, or recovering from injury. Many of the key factors underlying these processes are epigenetic regulators that enable the fine tuning or reprogramming of gene expression during development and regeneration in response to changes in the local microenvironment. These include chromatin remodelers, histone-modifying enzymes, covalent modifiers of DNA methylation, and RNA modification-mediated mechanisms. In this review, we will discuss the key components in each of these classes which are responsible for generating and maintaining oligodendrocyte myelination as well as potential targeted approaches to stimulate the regenerative program in developmental disorders and neurodegenerative diseases.
少突胶质细胞是形成髓磷脂神经鞘的关键细胞类型，能使中枢神经系统（CNS）实现高效的神经传导。少突胶质前体细胞分化为成熟的少突胶质细胞，并终生维持。这些细胞的生成、增殖、分化或维持出现缺陷，与从发育障碍到神经退行性疾病等一系列神经系统疾病有关，并限制了中枢神经系统损伤后的修复。了解这些过程的调控对于在发育过程中实现适当的髓鞘形成、预防疾病或从损伤中恢复至关重要。这些过程的许多关键因素是表观遗传调节因子，它们能够在发育和再生过程中响应局部微环境的变化，对基因表达进行微调或重编程。这些包括染色质重塑因子、组蛋白修饰酶、DNA甲基化的共价修饰因子以及RNA修饰介导的机制。在这篇综述中，我们将讨论这些类别中每一类的关键组成部分，它们负责产生和维持少突胶质细胞的髓鞘形成，以及在发育障碍和神经退行性疾病中刺激再生程序的潜在靶向方法。
