孤独症是一种严重影响儿童身心健康、具有显著临床异质性和病因异质性的神经发育障碍性疾病，是孤独症谱系障碍中最主要的类型。孤独症的致病机制研究一直进展缓慢，研究材料的限制是主要原因之一，而iPS技术的兴起为神经精神疾病的研究开辟了一条新的道路。本研究拟利用iPS技术，建立5-10个未发现特定遗传变异的患者来源的iPSCs和5个正常对照来源的iPSCs来进行以下研究：第一，诱导iPSCs形成拟胚体，在多个时间点检测神经系统发育相关基因的表达谱，通过对比研究以发现影响神经发育的关键基因；第二，将iPSCs定向分化成神经元，分析患者组与对照组在基因表达水平、神经元可塑性、突触连接功能等方面的差异，以发现细胞水平的病理表型；同时，对神经元进行转录组分析，结合表达谱分析结果，探索构建孤独症的分子调控机制和寻找分子标记。通过孤独症的iPSC模型研究，为孤独症的致病机理研究提供新的思路。

Autism is a neurodevelopmental disorder with significant clinical heterogeneity and etiological heterogeneity which seriously affects children's physical and mental health and it is the primary form of Autistic Spectrum Disorders (ASD). The pathogenic mechanism study of autism progress very slowly for a long period, one of the reasons is the limitation of research materials. However the rise of iPS technology in recent years has opened up a new path to the study of neuropsychiatric disorders. Therefore, this research program intends to use iPS technology to establish 5-10 iPSCs lines from patients in which none specific genetic variations were found and 5 iPSCs lines from normal controls for the following three aspects of research program. First, forced Embryoid Body formation was done use all iPSCs and then detecting the expression profile of the nervous system development related genes. After that control study was done to find pivotal genes in the neural development. Second, direct differentiation of all iPSCs into neurons to identify pathological phenotypes in the cellular level by evaluating gene expression, neuronal plasticity and synaptic links function differences between the two groups. Then combined the transcriptome’s analysis and expression profile results, to construct molecular regulation mechanism of autism and to search molecular markers. By the iPSC model study of autism, we may be able to provide new idea to the pathogenic mechanism study of autism.