Moyon Sarah, Casaccia Patrizia
Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY, USA.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Neuroscience Initiative Advanced Science Research Center, CUNY, New York, NY, USA.
Neurogenesis (Austin). 2017 Jan 31;4(1):e1270381. doi: 10.1080/23262133.2016.1270381. eCollection 2017.
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events. Based on the phenotypic characterization of mice with genetic ablation of DNA methyltransferase 1 () we conclude that DNA methylation is critical for efficient OPC expansion and for developmental myelination. Previous work suggests that in the context of diseases such as multiple sclerosis (MS) or gliomas, DNA methylation is differentially regulated in the CNS of affected individuals compared with healthy controls. In this commentary, based on the results of previous work, we propose the potential role of DNA methylation in adult oligodendroglial lineage cells in physiologic and pathological conditions, and delineate potential research approaches to be undertaken to test this hypothesis. A better understanding of this epigenetic modification in adult oligodendrocyte progenitor cells is essential, as it can potentially result in the design of new therapeutic strategies to enhance remyelination in MS patients or reduce proliferation in glioma patients.
少突胶质前体细胞（OPC）是中枢神经系统（CNS）的髓鞘形成细胞。在发育过程中，它们分化为成熟的少突胶质细胞（OL）并包裹轴突，为神经元提供营养和功能支持。这一过程受特定转录因子动态表达的调控，而转录因子的表达又受DNA甲基化等表观遗传标记的控制。在此，我们讨论最近的研究发现，即在发育性髓鞘形成过程中，少突胶质细胞谱系中的DNA甲基化水平受到差异调节，这影响了基因表达和可变剪接事件。基于DNA甲基转移酶1（）基因敲除小鼠的表型特征，我们得出结论，DNA甲基化对于少突胶质前体细胞的有效扩增和发育性髓鞘形成至关重要。先前的研究表明，在诸如多发性硬化症（MS）或神经胶质瘤等疾病的背景下，与健康对照相比，受影响个体中枢神经系统中的DNA甲基化受到差异调节。在本评论中，基于先前工作的结果，我们提出了DNA甲基化在生理和病理条件下对成年少突胶质细胞谱系细胞的潜在作用，并描述了为验证这一假设而可能采取的研究方法。深入了解成年少突胶质前体细胞中的这种表观遗传修饰至关重要，因为这可能会促成设计新的治疗策略，以增强MS患者的髓鞘再生或减少神经胶质瘤患者的细胞增殖。
