Meta-analysis of ALS hiPSC-astrocytes and correlation with A1 astrocytes. (A) Schematic depicting hiPSC-astrocyte differentiation in ALS mutant astrocytes (VCP, yellow; SOD1, blue; C9orf72, green; FUS, purple) and A1 hiPSC-astrocytes from five distinct differentiation protocols (red). Astrocytes underwent RNA sequencing and were analyzed for differential expression, with meta-analyses of ALS mutants (blue, top) and A1 astrocytes (red, bottom). We then ran a downstream bioinformatic analysis by mapping each gene's expression change in ALS versus control with that of A1 versus A0. (B) Volcano plot showing log₂ fold change in differential gene expression from the ALS meta-analysis for pan-ALS versus control astrocytes. Genes with significantly (FDR < 0.05) increased expression are shown in red, and those decreased in expression are shown in blue. (C) GO terms enriched in up-regulated (red) and down-regulated (blue) differentially expressed genes in pan-ALS versus control astrocytes. (D) Gene set enrichment analyses (GSEA) plot for glutamate uptake in pan-ALS astrocytes. (NES) Normalized enrichment score. Enrichment P-value < 1 × 10¹⁰. (E) Scatterplot of log₂ fold changes in gene expression in pan-ALS versus control astrocytes (x-axis) against A1 versus A0 astrocytes (y-axis). Black dashed line indicates linear regression correlation (Pearson's correlation R = + 0.1). Overlapping differentially expressed genes are colored red (up-regulated) and blue (down-regulated). (F) Venn diagram depicting the overlap of up-regulated (left) or down-regulated (right) genes (FDR < 0.05) in ALS versus control (blue) and A1 versus A0 (red). (G) Bar graph showing curated overrepresented functional categories (FDR < 0.05) by GO analysis of the genes commonly up-regulated (red) and co-down-regulated (blue) between A1 and ALS astrocytes.