Fig. 3
Quantification of the heterogeneous transcriptional response to IGF-1. a Principal component plot derived from neurotypical controls (CTL) either in baseline (H2O) conditions or treated acutely with IGF-1. Differentially expressed genes associated with acute IGF-1 treatment were used to generate PC axes that clearly separate H2O from IGF-1 and which can be used to assess additional datasets. b ASD samples either from baseline (H2O) or treated acutely with IGF-1 were projected onto the PC space calculated in (a) (ASD’). Each scatter plot inset is plotted along the same PC1 and PC2 axes as in (a) and are separated by sample condition (ASD-H2O, ASD-IGF-1, CTL-H2O, or CTL-IGF-1). pink dots = H2O, blue dots = acute IGF-1. The density of dots along the x-axis for each condition is plot as density plots above or below each scatter plot. The number of samples on the left or on the right side of PC1 = 0 are noted in the corners of the corresponding density plots. c The average PC1 value was calculated for each sample in H2O or after acute IGF-1 treatment and these values are plotted as boxplots. Each dot represents a sample with lines connecting the sample between the average PC1 value in H2O and the value after acute IGF-1 treatment. Samples which shifted to the right along PC1 are connected by a line colored in orange while samples that shifted to the left along PC1 are colored in blue. d The difference between the average PC1 value in acute IGF-1 and in H2O is plotted as a bar plot for each sample. Blue = CTL, red = ASD. e Correlation between the shift along PC1 from H2O to acute IGF-1 versus mean spontaneous neuronal activity as previously measured by multielectrode array (MEA) after IGF-1 treatment starting on day 37 [16]. Blue line = least squares regression fit, grey = confidence interval. Red dots = ASD samples, blue dots = CTL samples. f Correlation between the shift along PC1 and IGF1R expression either before (top) or after (bottom) IGF-1 treatment. Blue line = least squares regression fit, grey = confidence interval. Red dots = ASD samples, blue dots = CTL samples. g Quantitative RT-PCR validating IGF1R differential expression in ASD samples compared to CTL after IGF-1 treatment, p = 0.0037, Mann-Whitney U