Gene network analyses of transcriptomes obtained from these organoids revealed upregulation of genes involved in cell proliferation, neuronal differentiation, and synaptic assembly in ASD. Interestingly, GABAergic genes were strongly upregulated. Immunocytochemical analyses confirmed that, indeed, ASD patient-derived organoids exhibited an accelerated cell cycle and an overproduction of GABAergic inhibitory neurons compared to control organoids derived from the patients’ unaffected parents. This study further showed, using RNA interference, that increased expression of the master regulatory transcription factor FOXG1 in ASD patient-derived organoids is the cause for the increased production of GABAergic neurons. The data are intriguing, because the model clearly mimics a very early stage of cortical development, suggesting that what is modeled though hiPSC is predisposition to disease. Yet, the altered expression of gene network modules positively correlated with symptom severity, albeit in a small patient sample. It is possible that increased production of GABA is responsible for aberrantly increased synaptogenesis, as GABA functions as an excitatory neurotransmitter promoting activity-dependent synapse formation in prenatal development 139. The increase in synapse-related transcripts detected in hiPSC-derived organoids echoes a neuropathological study where
