Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah.
Neuroscience Graduate Program, University of Utah, Salt Lake City, Utah.
Dev Dyn. 2020 Jan;249(1):6-33. doi: 10.1002/dvdy.100. Epub 2019 Oct 1.
Autism spectrum disorders (ASDs) represent a spectrum of neurodevelopmental disorders characterized by impaired social interaction, repetitive or restrictive behaviors, and problems with speech. According to a recent report by the Centers for Disease Control and Prevention, one in 68 children in the US is diagnosed with ASDs. Although ASD-related diagnostics and the knowledge of ASD-associated genetic abnormalities have improved in recent years, our understanding of the cellular and molecular pathways disrupted in ASD remains very limited. As a result, no specific therapies or medications are available for individuals with ASDs. In this review, we describe the neurodevelopmental processes that are likely affected in the brains of individuals with ASDs and discuss how patient-specific stem cell-derived neurons and organoids can be used for investigating these processes at the cellular and molecular levels. Finally, we propose a discovery pipeline to be used in the future for identifying the cellular and molecular deficits and developing novel personalized therapies for individuals with idiopathic ASDs.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交互动受损、重复或限制性行为以及言语问题。根据疾病控制和预防中心的最新报告，美国每 68 名儿童中就有 1 名被诊断患有 ASD。尽管近年来 ASD 相关诊断和对 ASD 相关遗传异常的认识有所提高，但我们对 ASD 中受干扰的细胞和分子途径的理解仍然非常有限。因此，没有针对 ASD 患者的特定疗法或药物。在这篇综述中，我们描述了可能在 ASD 患者大脑中受到影响的神经发育过程，并讨论了如何使用患者特异性干细胞衍生的神经元和类器官来在细胞和分子水平上研究这些过程。最后，我们提出了一个发现管道，用于未来确定细胞和分子缺陷，并为特发性 ASD 患者开发新的个性化疗法。
