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Transcriptomic analysis of ATP6V1A knock-down and amyloid beta-treated neurons

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128367 | GEO | 2020/10/30

REPOSITORIES: GEO

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