Fig. 3
From: Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model
TOP motif mediated enhancement of growth factor synthesis. a Pie chart representation of the number of transcripts showing a significant change on the level of translation only (red; translation changes normalized by transcript level changes) or also on the transcriptional level (blue). b Detected de novo motif enrichment using the MEME tool (p < 0.05) within the 5’UTR of genes that showed significant TE changes in TSC2-deficient cells. c Density histograms for log2 changes of TE comparing heterozygous (left panel) and homozygous cells (right) with control. Red bars indicate transcripts with a known 5’-TOP motif and gray bars indicate all other detected transcripts. d Scatterplots of gene set enrichment analysis (GSEA) significance scores comparing transcriptional (x-axis) and translational (y-axis) changes in TSC2 heterozygous (left panel) and homozygous cells (right panel) versus control. Multiple pathways associated with protein synthesis (labeled) are positively regulated specifically on the translational level (FDR < 1E-4). e Measurement of translational activity in control, TSC2 heterozygous, and homozygous mutant cells after six weeks of differentiation. Protein synthesis was measured by flow cytometric detection of incorporation of FITC labeled amino acid analog O-propargyl-puromycin into newly synthesized protein. Histograms display the cell count for different levels of OPP incorporation. f Network of “vasculature development” and “tissue remodeling” related transcripts that show induction (logFC ≥ 2) of translation in the absence of TSC2 as determined by Fisher’s exact test (FDR < 0.01). Ellipse nodes represent transcripts and edges indicate either gene-biological process associations or protein-protein interactions. g Detection of angiogenic growth factors in cultures of TSC2-deficient and control cell lines (n=3) using protein arrays. Expression levels in control cells are set to 1 and significance of differential expression is determined by Student’s two tailed t-test, *p <0.05, **p <0.01, ***p <0.001