GSE128367
Transcriptomic analysis of ATP6V1A knock-down and amyloid beta-treated neurons
ATP6V1A plays a unique role in synapse function in neurons and we found decreased neuronal activity in ATP6V1A-deficient neurons. To characterize the molecular pathways regulated by ATP6V1A under both normal and stressed conditions, we generated hiPSC-derived NGN2-neurons with reduced ATP6V1A expression by CRISPRi knock-down (KD) and performed RNA-seq analysis on the wild-type and KD neurons which were subject to amyloid-beta or vehicle treatment. A number of gene ontology (GO)/pathways were identified in KD neurons without amyloid-beta treatment (proton transporting V-ATPase complex, phagosome acidification and trivalent inorganic cation transport were down-regulated, and mitochondrial protein complex up-regulated), while KD in amyloid-beta treated cells specifically resulted in down-regulation of cell adhesion, synapse assembly and structure/activity and up-regulation of UPR and ER stress response. Overall design: RNA from four groups of hiPSC-derived NGN2-neurons (designated WT-V and WT-Aß for vehicle-treated and amylod beta (Ab)-treated ATP6V1A wild-type (WT) neurons, respectively, and KD-V and KD-Aß for vehicle-treated and Aß-treated ATP6V1A KD neurons, respectively) were collected and loaded to RNA-sequencing analysis. There are five independent neuronal differentiation experiments in each group.