Extended Data Fig. 3: Various snRNA-seq and bulk RNA-seq analyses in 250-day-old mice reveal no significant changes in cell types other than oligodendrocytes and neurons. | Nature Aging

Extended Data Fig. 3: Various snRNA-seq and bulk RNA-seq analyses in 250-day-old mice reveal no significant changes in cell types other than oligodendrocytes and neurons.

From: Interleukin-12 signaling drives Alzheimer’s disease pathology through disrupting neuronal and oligodendrocyte homeostasis

Extended Data Fig. 3

a. Correlation of hippocampal snRNA-seq and bulk RNA-seq data with respect to the ratio in appearance of distinct cell types (r ≥ 0.75). b. Principal component analysis of biological replicates (bulk RNA-seq), each replicate is represented by one dot. WT mice cluster together, while APPPS1 and APPPS1.Il12b−/− mice are more scattered. c-d. MA plots comparing bulk gene expression of APPPS1 vs. WT mice (c) and of APPPS1.Il12b−/− vs. APPPS1 mice (d). e. Close-up of the astrocyte gene signatures derived from single-nucleus RNA-seq of WT, APPPS1 and APPPS1.Il12b−/− mice. f. Density plots illustrating the distribution of overall captured transcripts in WT vs. APPPS1 and APPPS1 vs. APPPS1.Il12b−/− mice. g. Feature plot of the distribution of Gfap transcripts in the astrocyte cluster and h. Gfap expression levels in WT, APPPS1 and APPPS1.Il12b−/−. i. Comparison of cellular proportions of three biological replicates per genotype determined by three independent methods, namely the previously published reference data set (red), snRNA-seq (green) and deconvolution of bulk RNA-seq data (dark blue). Of note, the deconvolution matched the other two reference data sets best in OPCs, microglia and oligodendrocytes. Boxplots show: middle, median; lower hinge, 25% quantile; 45 upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ± 1.5 x IQR. j. Cellular proportions gathered from deconvoluted bulk RNA-seq data across all three genotypes with three biological replicates each showed enhanced numbers of microglia in APPPS1 and APPPS1.Il12b−/− mice and a rescue of oligodendrocytes numbers in APPPS1.Il12b−/− mice. All df = 2, F = 6.053 for neurons, F = 3.783 for astrocytes, F = 83.238 for microglia, F = 26.317 for oligodendrocytes, F = 6.216 for OPCs, F = 7.182 for vascular cells, F = 0.499 for rest. One-way ANOVA with Holm-Bonferroni P value adjustment; boxplots show: middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ± 1.5 x IQR.

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