Modeling Rett Syndrome Using Human Induced Pluripotent Stem Cells
Modeling Rett Syndrome Using Human Induced Pluripotent Stem Cells
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DOI：
10.2174/1871527315666160413120156
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Akamatsu, Wado
中科院分区：
文献类型：
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作者：
Andoh-Noda, Tomoko;Inouye, Michiko O.;Akamatsu, Wado
Rett综合征（RTT）是一组神经发育障碍之一，其典型特征是X连锁基因MECP 2（甲基-CpG结合蛋白2）的缺陷。MECP 2基因编码一种多功能蛋白，参与转录抑制、转录激活、染色质重塑和RNA剪接。小鼠Mecp 2基因缺失揭示了包括RTT样表型在内的神经元功能障碍，为理解RTT的发病机制提供了一个很好的平台。由于MECP 2在RTT中的作用尚不完全清楚，目前尚无有效的药物治疗RTT。最近，人类诱导多能干细胞（hiPSC）技术已经提高了我们对神经系统和神经发育疾病（包括RTT）的认识，因为来源于RTT-hiPSC的神经元可用于疾病建模，以了解RTT表型并进行高通量药物筛选。本文综述了RTT的研究进展，包括MeCP 2的功能和小鼠RTT模型。此外，我们还介绍了使用hiPSC衍生的神经细胞进行RTT疾病建模的最新进展。
Rett syndrome (RTT) is one of a group of neurodevelopmental disorders typically characterized by deficits in the X-linked gene MECP2 (methyl-CpG binding protein 2). The MECP2 gene encodes a multifunctional protein involved in transcriptional repression, transcriptional activation, chromatin remodeling, and RNA splicing. Genetic deletion of Mecp2 in mice revealed neuronal disabilities including RTT-like phenotypes and provided an excellent platform for understanding the pathogenesis of RTT. So far, there are no effective pharmacological treatments for RTT because the role of MECP2 in RTT is incompletely understood. Recently, human induced pluripotent stem cell (hiPSC) technologies have improved our knowledge of neurological and neurodevelopmental diseases including RTT because neurons derived from RTT-hiPSCs can be used for disease modeling to understand RTT phenotypes and to perform high throughput pharmaceutical drug screening. In this review, we provide an overview of RTT, including MeCP2 function and mouse models of RTT. In addition, we introduce recent advances in disease modeling of RTT using hiPSC-derived neural cells.