Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question. Using RNAseq, we examined the transcriptome of iPSC-derived Neuronal Progenitor Cells (NPC) and neurons from a normocephalic ASD cohort composed mostly of high functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in NPC, and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons, while downregulated in brain samples. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target. mRNA profiles obtained by RNAseq of 12 samples of iPSC-derived NPC (6 controls/6 ASD individuals; total of 29 clones) and 9 samples of iPSC-derived Neurons (4 controls/5 ASD individuals; total of 19 clones). Transcriptome analysis was performed using dream algorithm (from variationPartition package), to find the differentially expressed genes between controls and patients, and WGCNA, to find co-expressed networks of genes that were dysregulated in these cell types in ASD.