Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
UCT Neuroscience Institute, Cape Town, South Africa.
Gene Ther. 2023 Sep;30(9):659-669. doi: 10.1038/s41434-022-00356-z. Epub 2022 Jul 5.
Autism spectrum disorders (ASDs) are a set of disorders characterised by social and communication deficits caused by numerous genetic lesions affecting brain development. Progress in ASD research has been hampered by the lack of appropriate models, as both 2D cell culture as well as animal models cannot fully recapitulate the developing human brain or the pathogenesis of ASD. Recently, cerebral organoids have been developed to provide a more accurate, 3D in vitro model of human brain development. Cerebral organoids have been shown to recapitulate the foetal brain gene expression profile, transcriptome, epigenome, as well as disease dynamics of both idiopathic and syndromic ASDs. They are thus an excellent tool to investigate development of foetal stage ASDs, as well as interventions that can reverse or rescue the altered phenotypes observed. In this review, we discuss the development of cerebral organoids, their recent applications in the study of both syndromic and idiopathic ASDs, their use as an ASD drug development platform, as well as limitations of their use in ASD research.
自闭症谱系障碍（ASD）是一组以社会和沟通缺陷为特征的疾病，这些缺陷是由影响大脑发育的多种遗传损伤引起的。由于缺乏合适的模型，自闭症研究进展一直受到阻碍，因为二维细胞培养和动物模型都不能完全再现发育中的人类大脑或 ASD 的发病机制。最近，大脑类器官已被开发出来，为人类大脑发育提供了更准确的三维体外模型。大脑类器官已被证明可以重现胎儿大脑的基因表达谱、转录组、表观基因组，以及特发性和综合征性 ASD 的疾病动态。因此，它们是研究胎儿期 ASD 发展以及可以逆转或挽救观察到的表型改变的干预措施的极好工具。在这篇综述中，我们讨论了大脑类器官的发展，它们在综合征性和特发性 ASD 研究中的最新应用，它们作为 ASD 药物开发平台的用途，以及它们在 ASD 研究中的使用限制。
