Extended Data Fig. 3: C9 ALS/FTD ALI-COs and patient samples show transcriptomic overlaps.
a, Dot plots represent the overlap of transcriptomic changes per cell-type between C9 ALI-COs at 150 DIV and human ALS patient-related samples20–25. Dot size indicates the percentage of cells expressing upregulated (yellow) and downregulated (purple) genes. Venn diagrams display the number of overlapping genes between C9-L1 and/or mutation-specific C9-L2 ALI-CO DEGs (in red) and ALS-related transcriptomic changes b, Heatmap shows log-fold expression changes per cell-type for significant C9-L1 (upper panel) or mutation-specific C9-L2 (lower panel) DEGs overlapping with each other (in red) or with ALS/FTD-related genes taken from the ALSoD GWAS database (https://alsod.ac.uk). c, Boxes, lines, whiskers display the quartile, median, min-max distribution (without the outliers) representing highly correlated genes defined by top differentially expressed module eigengenes (WGCNA) for astroglia and deep layer neurons (DLN) for 2 independent ALI-CO slice-pairs per group (4 ALI-CO slices per line). Two-sided Mann-Whitney-Wilcoxon test with Bonferroni correction. Bar graphs show corresponding top significantly enriched GO terms. d, Core interaction networks (STRING) of transcription factors (TFs) with predicted reduced activity (SCENIC), defined by the top 10 betweenness centrality score (Cytohubba/Cytoscape) for interacting TFs (nodes) and grouped into functional domains based on protein function (www.uniprot.org). Node size illustrates centrality score. See Supplementary Table 3 for detailed statistics.
