Ji Pengfei, Wang Xia, Xie Nina, Li Yujing
Department of Nutrition and Food Sciences, Texas A&M University, Room 218 Cater-Mattil, MS 2253 College Station, TX 77840, USA.
Department of Dermatology, Rizhao People's Hospital, Rizhao, Shandong Province 276826, China.
Stem Cells Int. 2018 Oct 10;2018:3256524. doi: 10.1155/2018/3256524. eCollection 2018.
Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.
大量新出现的证据表明碱基修饰与干细胞命运的决定（如增殖和分化）之间存在联系。在广泛研究的碱基修饰标记中，5-甲基胞嘧啶（5-mC）及其氧化衍生物（5-羟甲基胞嘧啶（5-hmC）、5-甲酰基胞嘧啶（5-fC）和5-羧基胞嘧啶（5-caC））在DNA和RNA中动态出现，并被认为是参与调节细胞生物学过程的重要表观遗传标记。近年来，DNA中的N6-甲基腺嘌呤修饰（m6dA）、mRNA中的（m6A）、tRNA和其他非编码RNA中的修饰已被定义为真核生物中另一种重要的表观遗传和表观转录组标记。mRNA的m6A修饰已在生物化学、分子和表型方面得到表征，包括对其甲基转移酶复合物（m6A写入器）、去甲基酶（m6A擦除器）和直接相互作用蛋白（读取器）的阐明，而关于DNA m6dA的信息有限。表观转录组和表观基因组中m6A的水平和图谱通过写入器和擦除器的精细协调，根据生命周期中自然编程的生长、发育和繁殖阶段进行精确和动态的调节。此外，在认识干细胞中异常m6A修饰与疾病（如癌症和神经退行性疾病）之间的联系方面也取得了进展。这些成就激励科学家进一步揭示干细胞发育的表观遗传机制，并剖析由干细胞发育异常导致的多种疾病的发病机制。这篇综述文章将重点介绍DNA和RNA的m6A甲基化修饰在干细胞调节和相关疾病发生中的作用的研究进展。此外，本文还将探讨未来的研究方向。
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