DNA methylation in oligodendroglial cells during developmental myelination and in disease.
DNA methylation in oligodendroglial cells during developmental myelination and in disease.
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DOI：
10.1080/23262133.2016.1270381
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Casaccia, Patrizia
中科院分区：
文献类型：
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作者：
Moyon, Sarah;Casaccia, Patrizia
少突胶质细胞祖细胞（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）和鞘轴突，为神经元提供营养和功能支持。这一过程受特定转录因子的动态表达调控，而转录因子的动态表达又受表观遗传标记（如DNA甲基化）的控制。在这里，我们讨论了最近的研究结果表明，DNA甲基化水平的差异调节在少突胶质细胞谱系在发育髓鞘形成，影响基因表达和选择性剪接事件。基于DNA甲基转移酶1（Dnmt 1）基因消融小鼠的表型特征，我们得出结论，DNA甲基化是有效的OPC扩增和发育髓鞘形成的关键。以前的工作表明，在多发性硬化症（MS）或神经胶质瘤等疾病的背景下，与健康对照组相比，受影响个体的CNS中DNA甲基化受到差异调节。在这篇评论中，基于以前的工作结果，我们提出了在生理和病理条件下，成年少突胶质细胞系细胞中DNA甲基化的潜在作用，并描绘了潜在的研究方法来测试这一假设。更好地了解这种表观遗传修饰在成年少突胶质细胞祖细胞是必不可少的，因为它可能会导致新的治疗策略的设计，以增强髓鞘再生MS患者或减少神经胶质瘤患者的增殖。
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 (Dnmt1) 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.