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Cerebral organoids as an in vitro model to study autism spectrum disorders

Abstract

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.

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Fig. 1: Generation of cerebral organoids.
Fig. 2: Changes occurring in idiopathic and syndromic ASDs compared to unaffected brains during development, as identified in cerebral organoids.

Data availability

All data as part of this study are included in this published article.

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Funding

This work was supported by the South African National Research Foundation (MG, Competitive Support for Unrated Researchers), The David and Elaine Potter Foundation (AR, The David and Elaine Potter Fellowship), and the University of Cape Town (MG, Research Development Grant).

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AR and MG wrote the paper. AR and MG contributed to the editing and approval of the final manuscript.

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Correspondence to Mubeen Goolam.

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Rabeling, A., Goolam, M. Cerebral organoids as an in vitro model to study autism spectrum disorders. Gene Ther (2022). https://doi.org/10.1038/s41434-022-00356-z

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