Fig. 2
snATAC-seq reveal cell-specific changes in chromatin accessibility in early vs. late Aβ pathology. (A) Uniform manifold approximation and projection (UMAP) dimensionality reduction after iterative LSI of snATAC–seq data from 12 sample pools. Each dot represents a single nucleus (n = 14,907), colored by its corresponding cluster (left) or cell type (right). Bar plot shows the number of cells per cluster, with corresponding cluster colors and assigned cell type (B) Genomic tracks display chromatin accessibility at a subset of marker genes used to annotate cell types in this study. (C) Estimated average hippocampus cell composition is shown for each time point and genotype. The n refers to the number of nuclei recovered after quality control filtering. Cell composition for WT at W8 is not presented due to low nuclei count (n = 88) (D) MA plots of differential snATAC-seq peaks reveal chromatin accessibility differences in excitatory neurons during early pathology (W3), while in late pathology (W24), these differences are exclusive to inhibitory neurons. (E) Significant gene ontology (GO) terms associated with differentially accessible regions in inhibitory neurons at W24.
