Fig. 2

Whole transcriptome analysis of QPRT-KO cells and control cell lines. a Heatmap of differentially expressed genes. Upon KO of QPRT, 269 genes were significantly differentially expressed between both of the KO and the eCtrl cell line (FDR ≤ 0.05) but not between the controls (wild-type and eCtrl, FDR > 0.1). Overall, ins395A descriptively shows stronger effects than del268T. b GO term enrichment for differentially regulated genes. Upregulated genes were associated with GO terms including neurotransmitter secretion, negative regulation of cell growth and negative regulation of cytoskeleton organization (all p < 0.05; Additional file 3: Table S3). Genes downregulated upon QPRT-KO were enriched for GO terms involved in processes of neuronal development (positive regulation of neuron differentiation, positive regulation of dendritic spine development, and synapse organization (all p < 0.04)) and neurotransmitter transport (potassium transport, as well as glutamatergic processes like glutamate secretion and regulation of glutamate receptor signaling pathway (all p < 0.05)). Deregulated genes were enriched for processes like neurotransmitter secretion and brain development (all p < 0.05; Additional file 3: Table S3). All p values account for the hierarchical structure of the gene ontology (GO) and can thus be considered as corrected for multiple testing. c Regulation of the dark grey gene set. This module was identified as QPRT-KO associated module harboring genes downregulated upon QPRT-KO when comparing both KO cell lines to wild-type and eCtrl cells (all p < 8E−07). GO term enrichment analysis of this module again revealed processes involved in brain development and synaptic transmission and plasticity (p < 0.05), confirming the association of QPRT-KO with neuronal development