Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons.
Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons.
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通过将人类尿液细胞快速转化为功能神经元来模拟神经疾病
DOI：
10.1155/2016/2452985
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发表时间：
2016
影响因子：
4.3
通讯作者：
Wu ZY
中科院分区：
文献类型：
--
作者：
Zhang SZ;Ma LX;Qian WJ;Li HF;Wang ZF;Wang HX;Wu ZY
体细胞可以通过特定因子和/或microrna的异位表达直接转化为功能神经元。自从首次报道将小鼠胚胎成纤维细胞转化为功能性神经元以来，出生后的小鼠和人类成纤维细胞、星形胶质细胞、肝细胞和周细胞来源的细胞已经在体外和体内转化为功能性多巴胺能和运动神经元。然而，获得所有这些材料是侵入性的。在目前的研究中，我们提供了一种非侵入性的方法，通过在人尿细胞中过度表达转录因子Ascl1、Brn2、NeuroD、c-Myc和myt11来获得直接重编程的功能神经元。这些诱导的神经元（iN）细胞可以表达多种神经元特异性蛋白并产生动作电位。此外，威尔逊氏病（WD）患者的尿细胞也可以直接转化为神经元。总之，从非神经谱系中生成In细胞是一种可行且合适的神经系统疾病建模方法。
Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.