Genome-wide gene expression prolifing post-valproic acid exposure in human forebrain organoids

Human forebrain organoids (day 42) derived from U1M and U2F iPS cell lines were exposed with or without 1 mM valproic acid (VPA) for 72h. Organoids were then randomly selected for RNA sequencing, we found that differentially expressed genes (DEGs) induced by VPA exposure that shared in both U1M and U2F were enriched with neural development, synaptic transmission, calcium and potassium signaling pathways. The DEGs were also significantly enriched with autism spectrum disorder (ASD)-associated genes, including genes dysregulated in brains or organoids derived from ASD patients, and known ASD risk genes, as well as genes in ASD risk-associated gene coexpression modules. Overall design: We generated human forebrain organoids from U1M and U2F iPS cell lines. On day 42, human forebrain organoids derived from both U1M and U2F were exposed with or without 1 mM VPA for 72h. Three organoids in each group were randomly selected for RNA-seq (Illumina NovaSeq 6000, paired-end 150 bp) to identify genes affected by VPA exposure. DEGs (adjusted P value < 0.05) that identified in both U1M and U2F were used for Gene Ontology and KEGG pathway analysis.