Fig. 3: The neural progenitor/immature neuron transition appears as a key stage of neuronal development in RTS.

a PCA of gene expression data for the 1000 most variable genes for all patients and controls. The two major components are shown (PC1, x-axis; PC2, y-axis). b Heatmap of control- and RTS-derived neurons at D10 (red), D20 (green), and D60 (blue), showing that RTS patients cluster separately from controls at D20, suggesting a different expression profile at this transition time point between neural progenitors and immature neurons. Only genes with padj < 0.01 and |log2FC| ≥ 1 are shown. c Venn diagram comparing the DEGs found at the three differentiation time points in RTS versus control cells. The comparison is performed for all (left), upregulated (middle) and downregulated (right) DEGs. d Volcano plot of differentially expressed genes (DEG) during neuronal differentiation at D10 (left), D20 (middle), and D60 (right) comparing expression in all patients versus controls. The x-axis corresponds to the log2Foldchange. The significance threshold is set at |log2Foldchange| ≥ 1. The y-axis corresponds to the −10log of the adjusted pvalue that indicates the level of expression difference. Blue dots correpond to significantly deregulated genes in patients compared to controls. e Representation of the evolution of the number of upregulated and downregulated DEGs in RTS patients vs controls during neuronal differentiation, showing a substantial increase of DEGs with a reversal of the upregulated vs. downregulated DEGs ratio transiently at D20.