Fig. 1: Differential gene expression upon PTBP2 depletion in iPSC-neurons.
From: Mapping PTBP2 binding in human brain identifies SYNGAP1 as a target for therapeutic splice switching
a Cartoon schematic of experimental design. Created with BioRender.com. b Western blot of PTBP protein levels at different stages of neuronal maturation. c Validation of PTBP2 depletion using “gapmer” ASOs in iPSC-neurons. (Left) qPCR and (Top and bottom right) Western blot of PTBP2. NegA, negative control gapmer. d Volcano plot of differential gene expression comparing untreated and PTBP2 KD iPSC-neurons. e SynGO enrichment analysis of curated synaptic genes differentially expressed upon PTBP2 KD (padj <0.05, |fold-change|>= 1.15) relative to a background set of brain-expressed genes represented as a sunburst plot. (Top) Biological Process, 224 genes. (Bottom) Cellular Component, 271 genes. f Category netplot (clusterProfiler) of the top synapse-associated GO terms overrepresented upon PTBP2 KD (Biological Process, PTBP2 KD vs. untreated iPSC-neurons) relative to a background of all genes evaluated. Color indicates fold-changes of differentially expressed synapse-associated genes (padj <0.05, |fold-change|> = 1.15). Size indicates number of genes in term. n = 3 biological replicates for iPSC-neurons RNA-seq data sets. b, c Data are represented as mean values ± SEM. All data points represent independent biological replicates. b, c (n = 3). b One-way ANOVA with Dunnett’s multiple comparison test vs. iPSCs. c, one-way ANOVA with Dunnett’s multiple comparison test vs. mock-treated cells (−). Source data are provided as a Source Data file. DGE differential gene expression, KD knock-down, FC fold change, PSD postsynaptic density, SV synaptic vesicle.
