Inducible pluripotent stem cells (iPSCs) are being used to model brain disorders across the continuum of neurodevelopment, neurodegenerative, and neuropsychiatric disease allowing for the mechanistic unraveling of the neurological disease state. Subsequently, there is a diverse array of cell model systems that can be used for target validation, pharmacodynamic endpoint development, and high-throughput/content assay development and screening. However, to successfully model neurological disorders with iPSCs, the disease-relevant neuron must be first identified, and it is critical to have the appropriate neuronal progenitor cell derivation and neuron differentiation protocols available to produce desired neuronal phenotypes. Moreover, special considerations are necessary if adaptation to high-throughput/content assay systems is anticipated. Discussed here are the three-dimensional embryoid body-neural rosette and two-dimensional monolayer methodologies to derive iPS neural progenitor cells and neurons with a specific focus on cortical neurons. Outlined are some of the commonalities, advantages, and disadvantages associated with both methodologies.

中文翻译：

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用于药物发现应用的神经祖细胞衍生方法。

诱导性多能干细胞（iPSC）被用于在整个神经发育，神经退行性疾病和神经精神疾病的连续性中对脑部疾病进行建模，从而可以对神经疾病状态进行机械分解。随后，有各种各样的细胞模型系统可用于靶标验证，药效学终点开发以及高通量/含量测定开发和筛选。但是，要成功地用iPSC建模神经系统疾病，必须首先确定与疾病相关的神经元，并且至关重要的是拥有合适的神经元祖细胞衍生和神经元分化方案，以产生所需的神经元表型。此外，如果期望适应高通量/含量测定系统，则需要进行特殊考虑。这里讨论的是三维胚状体-神经玫瑰花结和二维单层方法，以衍生iPS神经祖细胞和神经元，特别关注皮质神经元。概述了与这两种方法相关的一些共性，优点和缺点。