RNA-Seq of iPSC-derived neurons

Induced pluripotent stem cells (iPSC)-derived neurons were used to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) to mimic neural activity and its effects were assessed by RNA sequencing. Our results revealed the involvement of both protein-coding and long non-coding RNAs as well as a subset of human-specific genetic variants in response to neuronal activation. This study helps validate iPSCs as a valuable resource for the study of human neuronal networks.Because there is a strong association between cannabis use and schizophrenia, we treated neurons derived from hiPSCs with ?9- tetrahydrocannabinol (THC) either in a single dose (acute treatment) or 5 doses (chronic treatment) and followed this by activating treated and untreated neurons with KCl. RNA sequencing analyses revealed that THC administration severely dampened the neuronal transcriptional response following KCl treatment. The blunted response in THC-treated neurons closely resembles that previously observed in schizophrenia-associated iPSC-derived neurons. Results may help explain the significant phenotypic association between cannabis use and schizophrenia.