Fig. 5

Identifying conserved disease-modifying gene expression signatures and neuroprotective transcripts. A Venn diagram representing differentially expressed genes (DEGs) identified in the human C9-disease and C9-treated groups. B Identification of a human disease-modifying gene expression signature. Heatmap representing the computed fold changes (FC) for the common human transcripts modulated in both C9-disease and C9-treated groups. Red labels show down-regulated transcripts while green depicts upregulated transcripts. C Venn diagram representing differentially expressed genes (DEGs) identified in the Drosophila C9-disease and C9-treated groups. D Identification of a Drosophila disease-modifying gene expression signature. Heatmap representing the FC for the common Drosophila transcripts modulated in both C9-disease and C9-treated groups. Red labels show down-regulated transcripts while green depicts upregulated transcripts. E Gene ontology analysis of conserved differentially-expressed transcripts identified in the human and Drosophila disease-modifying gene expression signatures carbohydrate metabolism, ion transport and response to stress as commonly altered in disease and manipulated upon neuroprotection. F Heatmap representing the computed fold changes for the orthologous genes in the disease-modifying signatures. Red labels show down-regulated transcripts while green depicts upregulated transcripts. G Heatmap representing the computed fold neuroprotective changes for the orthologous genes in the C9-treated groups. Red labels show down-regulated transcripts while green depicts upregulated transcripts. H qRT-PCR quantification of Drosophila SK and human KCNN1 orthologous transcripts. Relative expression levels of SK mRNA was quantified for the indicated Drosophila lines in biological triplicates following normalization to Tub84b mRNA levels and to 100% for G4C2x3 + C-RNAi Drosophila heads (mean ± SEM; one-way ANOVA with Tukey’s correction for multiple comparisons; ****: p < 0.0001; N (qRT-PCR reactions) = 3). Relative expression levels of KCNN1 mRNA was quantified in whole-cell patient-derived neurons in biological triplicates following normalization to U1 snRNA levels and to 100% for healthy neurons treated with C-RNAi (mean ± SEM; one-way ANOVA with Tukey’s correction for multiple comparisons, ***: p < 0.001, ****: p < 0.0001; N (qRT-PCR reactions) = 3)