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Lab Reports
September 1, 2015

Organoids Help Uncover Possible Mechanisms of Autism

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Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA. 2015;314(9):866. doi:10.1001/jama.2015.10607

Using induced pluripotent stem cells (iPSCs) from patients with autism spectrum disorder (ASD) and unaffected family members to grow 3-dimensional neural cultures (organoids) that recapitulate first trimester brain development, investigators at Yale University in New Haven have gained insights into early development of the autistic brain (Mariani J et al. Cell. 2015;162[2]:375-390).

Compared with brain organoids derived from unaffected family members, those from 4 patients with idiopathic ASD displayed a variety of neurodevelopmental differences, including altered expression of genes controlling neuronal development, up-regulated cell proliferation, overproduction of inhibitory neurons, and altered synaptic development. Autism spectrum disorder–derived organoids also appeared to overproduce inhibitory GABAergic neurons. By attenuating the expression of a single gene encoding the transcription factor FOXG1, the researchers were able to restore differentiation of the inhibitory neurons to normal levels.

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