Fig. 2: HTS identifies PP as a SON-dependent nuclear speckle rehabilitator.
From: SON-dependent nuclear speckle rehabilitation alleviates proteinopathies
a Workflow detailing our initial drug screen and subsequent steps to identify nuclear speckle rehabilitators. b Dose-dependent effect on nuclear speckles morphology by PP, with a representative image of nuclear speckles under DMSO or 0.1 µM of PP (n = 25 ~ 57 cells collected evenly across three separate wells for each treatment). c Box and whiskers plot (box and whiskers represent 25th to 75th, and 10th to 90th percentile, respectively, with center line representing the median) of the quantification of total area-normalized perimeter of nuclear speckles in control and 1 µM PP per cell (n = 49 and 52 cells for DMSO and PP, respectively, quantified from three separate imaging experiments). d GSEA showing a similar transcriptome signature between PP-upregulated genes and 461 genes further amplified by SON OE during ER stress. e GSEA analysis showing a similar transcriptome signature between PP-downregulated genes and 901 genes further repressed by SON OE during ER stress. f Volcano plot showing fold change by PP versus log transformed P values. Genes induced or repressed by at least 1.41-fold with a P value smaller than 0.05 are boxed. g GO analysis of differentially expressed genes by PP. h Representative images and quantification of sphericity of GFP signal from GFP::SRSF2 MEFs with scrambled or Son siRNA treated with DMSO or increasing concentration of PP for 25 h (n = 51 ~ 81 and 31 ~ 62 cells for scrambled and Son siRNA, respectively, quantified from two separate imaging experiments). i Log2 normalized fold change in response to PP treatment (0.3 µm) for 24 h in control and SON KD MEFs (n = 3 biologically independent samples). All data mean ± S.E.M. Statistical tests used: unpaired two-tailed Student’s t-test for (c, i). Kruskal-Wallis test for (b) and Ordinary one-way ANOVA for h. The corresponding quantified data points for (c, h) each annotated to indicate their respective independent experiments, are provided in the source data file.
