The controlled differentiation of pluripotent stem cells (PSCs) into neurons and glia offers a unique opportunity to study early stages of human central nervous system development under controlled conditions in vitro. With the advent of cell reprogramming and the possibility to generate induced pluripotent stem cells (iPSCs) from any individual in a scalable manner, these studies can be extended to a disease- and patient-specific level. Autism spectrum disorder (ASD) is considered a neurodevelopmental disorder, with substantial evidence pointing to early alterations in neurogenesis and network formation as key pathogenic drivers. For that reason, ASD represents an ideal candidate for stem cell-based disease modeling. Here, we provide a concise review on recent advances in the field of human iPSC-based modeling of syndromic and non-syndromic forms of ASD, with a particular focus on studies addressing neuronal dysfunction and altered connectivity. We further discuss recent efforts to translate stem cell-based disease modeling to 3D via brain organoid and cell transplantation approaches, which enable the investigation of disease mechanisms in a tissue-like context. Finally, we describe advanced tools facilitating the assessment of altered neuronal function, comment on the relevance of iPSC-based models for the assessment of pharmaceutical therapies and outline potential future routes in stem cell-based ASD research.

中文翻译：

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用于研究自闭症谱系障碍相关神经元功能障碍的人类干细胞模型


多能干细胞 (PSC) 受控分化为神经元和神经胶质细胞，为在体外受控条件下研究人类中枢神经系统发育的早期阶段提供了独特的机会。随着细胞重编程的出现以及以可扩展的方式从任何个体生成诱导多能干细胞 (iPSC) 的可能性，这些研究可以扩展到特定于疾病和患者的水平。自闭症谱系障碍 (ASD) 被认为是一种神经发育障碍，大量证据表明神经发生和网络形成的早期改变是关键的致病驱动因素。因此，自闭症谱系障碍是基于干细胞的疾病模型的理想候选者。在这里，我们对基于人类 iPSC 的综合征型和非综合征型 ASD 建模领域的最新进展进行了简要回顾，特别关注解决神经元功能障碍和连接改变的研究。我们进一步讨论了最近通过脑类器官和细胞移植方法将基于干细胞的疾病模型转化为 3D 的努力，这使得能够在类组织环境中研究疾病机制。最后，我们描述了促进评估神经元功能改变的先进工具，评论了基于 iPSC 的模型与药物治疗评估的相关性，并概述了基于干细胞的自闭症谱系障碍研究的潜在未来路线。