Fig. 3: Full-body APOE allele switching drives AD-relevant transcriptomic changes in multiple CNS cell types. | Nature Neuroscience

Fig. 3: Full-body APOE allele switching drives AD-relevant transcriptomic changes in multiple CNS cell types.

From: APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition

Fig. 3: Full-body APOE allele switching drives AD-relevant transcriptomic changes in multiple CNS cell types.

a, Uniform manifold approximation and projection (UMAP) of all 85,701 cells analyzed, classified based on canonical gene expression markers into 12 cell types (APOE4s2G, n = 3; APOE4s2, n = 3; E2-TR, n = 3, E4-TR, n = 2; all females). b, Number of DEGs between APOE4s2G and Cre− APOE4s2 controls according to cell type (Padj = <0.001). c, Venn diagrams revealing commonality of DEGs in the APOE4s2G versus APOE4s2 and E2-TR versus E4-TR datasets. d–g, Upregulated and downregulated GO terms associated with DEGs from astrocytes (d), oligodendrocytes (e), microglia (f) and endothelial cells (g). The cutoff value for significance was set at a false discovery rate (FDR)-adjusted P value of 0.05. h, Pie charts visualizing the categorical distribution of APOE switch-related GO terms into AD-related pathways. Upregulated (left) AD pathways account for 24%, while downregulated (right) AD pathways account for 21% of total downregulated GO terms. i, Overlap of the APOE switch transcriptomics dataset with five relevant gene lists from AD-related transcriptomic studies. DAA, disease-associated astrocyte; OPC, oligodendrocyte precursor cell; Transcription corep. binding, transcription corepressor binding; VLC, vascular leukocyte.

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