Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.
Neuropathol Appl Neurobiol. 2020 Feb;46(1):6-27. doi: 10.1111/nan.12608. Epub 2020 Mar 9.
Neural development requires the orchestration of dynamic changes in gene expression to regulate cell fate decisions. This regulation is heavily influenced by epigenetics, heritable changes in gene expression not directly explained by genomic information alone. An understanding of the complexity of epigenetic regulation is rapidly emerging through the development of novel technologies that can assay various features of epigenetics and gene regulation. Here, we provide a broad overview of several commonly investigated modes of epigenetic regulation, including DNA methylation, histone modifications, noncoding RNAs, as well as epitranscriptomics that describe modifications of RNA, in neurodevelopment and diseases. Rather than functioning in isolation, it is being increasingly appreciated that these various modes of gene regulation are dynamically interactive and coordinate the complex nature of neurodevelopment along multiple axes. Future work investigating these interactions will likely utilize 'multi-omic' strategies that assay cell fate dynamics in a high-dimensional and high-throughput fashion. Novel human neurodevelopmental models including iPSC and cerebral organoid systems may provide further insight into human-specific features of neurodevelopment and diseases.
神经发育需要协调基因表达的动态变化，以调节细胞命运决定。这种调节受到表观遗传学的强烈影响，即基因表达的可遗传变化不能仅通过基因组信息来解释。通过开发能够检测表观遗传学和基因调控各种特征的新技术，人们对表观遗传调控的复杂性的理解正在迅速出现。在这里，我们提供了几种常见的表观遗传调控模式的广泛概述，包括 DNA 甲基化、组蛋白修饰、非编码 RNA 以及描述 RNA 修饰的表观转录组学，这些都在神经发育和疾病中。人们越来越认识到，这些不同的基因调控模式不是孤立运作的，而是动态相互作用的，并沿着多个轴协调神经发育的复杂性质。未来研究这些相互作用的工作可能会利用“多组学”策略，以高维、高通量的方式检测细胞命运的动态变化。新型人类神经发育模型，包括 iPSC 和大脑类器官系统，可能为神经发育和疾病的人类特异性特征提供进一步的见解。
