Fig. 3: C9 ALI-COs at 150 DIV show similarities to ALS-related transcriptional profile, cell stress pathways and adaptive changes.
a, Number of DEGs per cell type in C9-L1 versus H-L1/H-L2 control ALI-COs (upper) and C9-L2 versus mutation-corrected isogenic ISO-L2 control (lower) ALI-COs (four slices per organoid line). b, Venn diagrams display the number of overlapping genes between C9-L1 and C9-L2 ALI-CO DEGs and ALS-related transcriptomic changes. c,d, Dot plots represent the overlap in transcriptomic changes between astroglia (c) or DLNs (d) in control or C9 ALI-COs and samples from patients with ALS20,21,22,23,24,25. The dot size indicates the percent of cells expressing overlapping upregulated (yellow) and downregulated (purple) genes. Gene names in red indicate overlapping genes between C9-L1 ALI-CO and C9-L2 ALI-CO (mutation-specific) DEGs and ALS patient sample-related transcriptomic changes. e, Venn diagrams represent top astroglia- (upper) and DLN-related (lower) GO terms that overlap between C9-L1 ALI-CO and C9-L2 ALI-CO (mutation-specific) DEGs. f, Boxes, lines, whiskers display the quartile, median and minimum–maximum distribution (without the outliers) representing top differentially expressed module eigengenes (WGCNA) for astroglia and DLNs in two H-L2, 2 H-L1, 2 C9-L1, 2 C9-L2, 2 ISO-L2 independent ALI-CO slice-pairs (4 slices per line), respectively. Two-sided Mann–Whitney–Wilcoxon test with Bonferroni correction. Bar graphs show the corresponding top significantly enriched GO terms. g, Core interaction networks (STRING) of TFs with predicted activity (SCENIC) defined by the top 10 betweenness centrality score (Cytohubba in Cytoscape) for interacting TFs (nodes) and grouped into functional domains based on gene/protein function (https://www.uniprot.org). Node size illustrates centrality score. See Supplementary Table 3 for detailed statistics.
