Extended Data Fig. 10: Validation of cell-type composition and spatial gene expression in TauPS2APP mice.
a, Gene expression heatmaps for representative markers aligned with each top-level cell type of 64-gene (validation) datasets. Expression for each gene is z-scored across all genes in each cell. b, UMAP plot visualizing a non-linear dimensionality reduction for the transcriptomic profiles of 36,625 cells from four samples of the validation dataset. Cells are colored as in (a). c, Spatial atlas of top-level cell types in cortex and hippocampus regions of four samples in the 64-gene dataset. Scale bars, 100 µm. d, Barplot showing the number of cells per top-level cluster in 2,766-genes and 64-genes datasets. Data are represented as mean with 95% CI. Student’s t-test, two-tailed *P < 0.05, **P < 0.01. e,f, UMAPs showing the Gfap gene expression (e) and normalized GFAP protein signal (f) in 64-genes validation dataset. g, Violin plot shows the normalized GFAP protein signal level in the astrocyte cell population (N = 3,423 cells) compared to others (N = 33,202 cells). Box plots depict the median (center) and interquartile range (IQR, bounds of the box), with whiskers extending to the maxima/minima or to the median ± 1.5× IQR. Two-sided t-test, ****P < 0.0001. h, Representative immunofluorescence images in the brain section of 64-gene validation samples (N = four independent animals). Astrocytes were marked by yellow arrows in the raw data. i, Cell-type composition around Aβ plaque at different distance intervals in both eight- and 13-month samples of the 64-gene validation dataset. Asterisks denote significantly enriched cell types in each distance interval. One-sided one-sample t-test, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. overall cell density. j, Barplot showing the cell density of astrocyte, microglia, oligodendrocyte and OPC in hippocampus alveus region in the 2,766- gene samples and validation samples. k, Matrix plot showing the row-wise scaled expression values of top significantly altered (rank by p-value) DEGs of glial cells and neuronal cells from TauPS2APP versus control samples. l,m, Matrix plot showing PIG that overlapped with 64-gene in each distance interval around the Aβ plaque in the eight-month (l) and TauPS2APP 13-month sample (m) of the 64-gene validation dataset. Colored by row-wise z-score.
