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. Author manuscript; available in PMC: 2022 Jul 7.
Published in final edited form as: Nat Neurosci. 2020 Apr 27;23(6):701–706. doi: 10.1038/s41593-020-0624-8

Figure 1. A cell atlas of the hippocampus reveals unique disease-associated astrocytes in AD.

Figure 1.

(a) Overview of the experimental strategy. (b) Cell map of mouse hippocampus in WT and AD. tSNE embedding of 54,769 single nucleus RNA profiles from hippocampi of 7-month-old male mice, four WT and four 5xFAD (AD); colored by cluster. Right: Hierarchical cluster tree. (c) Changes in frequency of multiple cell types in AD. Right: Boxplot showing fraction of nuclei per cluster in WT and AD mice. Box: 75% and 25% quantile. Line: Median. Dots: individual samples. Left: Log ratio of average fraction in WT vs. AD. Asterisks: Statistically significant differences between AD and WT (n=8 animals, two-sided p-value<0.01, paired t-test or Wilcoxon test for non-normally distributed samples). (d) A continuous trajectory across three major astrocyte states in AD and WT brains. Diffusion map embedding of 7,345 WT and AD astrocytes, colored by cluster (grey: cells of other conditions). The three end states are marked: Gfap-low/high and DAA. Inset: Map colored by Gfap expression level. (e) Marker genes of astrocyte states. Expression level (color scale) of marker genes across clusters and the percentage of cells expressing them (dot size). (f) An increase in frequency of DAAs and reduction in frequency of homeostatic Gfap-low astrocytes in AD. Boxplot (as in c) showing the fraction of nuclei per cluster in WT and AD. Asterisks: Statistically significant differences between AD and WT (n=8 animals. Statistical test as in c). Similar proportions found in cortical brain region and in female mice, Extended Data Fig. 4.