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Fig. 1 | Molecular Neurodegeneration

Fig. 1

From: Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease

Fig. 1

Disease associated microglia resemble atherosclerotic foam cells and signature gene expression reveals partial TREM2 dependence (A) UMAP plot displaying clustering of TREM2WT/WTxMGs isolated from 7-month-old 5X-hCSF1 mice (n=3 mice; 22,107 cells; WT xMGs per mouse (5987, 7876, 8244) and R47H xMGs per mouse (3939, 5571); B UMAP plot displaying clustering of TREM2R47H/R47HxMGs isolated from 7-month-old 5X-hCSF1 mice (n=2 mice; 9,510 cells); C A dot plot reveals top marker genes that are significantly up- or downregulated for each of the seven clusters (FDR-adjusted p-value < 0.01); (D) Barplot displaying the average percentage of cells making up the 7 unique xMG clusters; E Volcano plot displaying genes significantly up- and downregulated when comparing all TREM2R47H/R47H cells vs. all TREM2WT/WT cells; F-G UMAP plots displaying the module scores for 7 key DAM signature genes and 29 Foam cell signature genes identified in (Fernandezet al., [41]) (Additional File 1) in TREM2WT/WT (F) and TREM2R47H/R47H(G); H A dot plot reveals foam cell genes are particularly enriched in the DAM cell cluster (FDR-adjusted p-value < 0.01). Size of the circles indicate the percentage of cells expressing that gene and color indicates average expression levels; I Violin plots demonstrate foam cell signature genes are particularly enriched in the DAM cell cluster vs. other clusters, and are significantly (adjusted p-value < 0.01; LFC≥0.01) albeit subtly downregulated in R47H cells when comparing all TREM2R47H/R47H (blue) vs. all TREM2WT/WT cells (green) via pseudobulk analysis (Additional File 1)

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