Extended Data Fig. 4: Sox9 expression and gene regulation in APP^NLGF astrocytes.

a. Top 5 related phenotype-genotype integrator association (PhenGenI) analyses of the DEGs between 18 month-old WT astrocytes and Sox9cKO astrocytes. b. UMAP plot of total cell clusters from human anterior hippocampal cortex of age-matched controls (Human Con) and human AD patients (Human AD). c, d. ALDH1L1 expression (c) and SOX9 (d) in the total cell clusters of Human Con and Human AD. e. Table for information on human AD samples with age-matched controls. f. Representative confocal Z-stack images of GFAP (green) and Aβ (red) in the hippocampus of human AD and Human Con. Scale bars, 20 µm. g. Representative confocal Z-stack images of Aβ (green) and Lamp1 (red) in the hippocampus of the WT mouse and APP^NLGF mouse from 2 month-old to 8 month-old. Scale bars, 500 µm. h, i. Representative confocal Z-stack images of GFP (green), Aβ (purple), and Sox9 (red) in the hippocampus of 4 month-old WT (h) and 4 month-old APP^NLGF mouse (i). Scale bars, 50 µm (full image) and 20 µm (each region). j. Quantification graphs of Sox9 intensities (from each area; left panel, by distance from plaque; right panel) in astrocytes of each group. n = 5 mice of each group. k. Heatmaps comparing Sox9-ChIP at 4 kb from the peak center in hippocampal astrocytes from 6-month-old WT; Aldh1l1-GFP (Young_Sox9) and 18-month-old WT; Aldh1l1-GFP (Old_Sox9), and 6-month-old APP^NLGF; Aldh1l1-GFP (APP^NLGF_Sox9). l. A Venn diagram reveals the number of shared genes from each ChIP dataset. m. GO analysis for specific genes of each group. n, o. UMAP plot of total cell cluster (n) and astrocyte clusters (o) from scRNAseq between WT and APP^NLGF at 6 months. One-way ANOVA followed by Tukey’s comparisons test (j) was used for analysis. The mean ± s.e.m. ns: not significant.

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