Extended Data Fig. 5: Exercise regulates DAM-like microglia in AD mouse models. | Nature Neuroscience

Extended Data Fig. 5: Exercise regulates DAM-like microglia in AD mouse models.

From: Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing

Extended Data Fig. 5

a, b, Quantification of IBA-1+ microglia per mm2 in the dorsal DG (a, two-way ANOVA, Exercise **P = 0.0021, Genotype ****P < 0.0001, Exercise x genotype **P = 0.0031, followed by Fisher’s LSD, WT-Sed vs Run ns P = 0.8979, APP/PS1 Sed vs Run ***P = 0.0001) and ventral DG (b, two-way ANOVA, Exercise *P = 0.0495, Genotype ****P < 0.0001, Exercise x genotype n.s. P = 0.1564) (WT-Sed n = 6, WT-Run n = 6, APP/PS1-Sed n = 5, APP/PS1-Run n = 6). c, UMAP representation of marker genes for perivascular macrophages (Mrc1, Cd163, Cd74), monocytes (S100a4), B cells (Cd79b, Rag1), T cells (Trbc2, Cd3g), and natural killer cells (Nkg7). Color represents expression level according to the scale bar on the right. d, Cell composition in percentage for each subcluster shown in Fig. 4g–i. Two-way ANOVA, Exercise n.s. P = 0.9956, Genotype ****P < 0.0001, Exercise x genotype n.s. P = 0.8881. e, Heatmap shows the normalized mean expression (z-score) group of IFN, MHC, and Cyc-M microglia genes reported by Chen et al. in our dataset. f, Dot plots showing microglia subcluster 1 markers. In each, the hue and size of the dot represent the mean expression and fraction of non-zero count nuclei, respectively. g, Violin plots of gene signatures for DAM (Irf8, Trem2, Igf1, Axl, and Csf1) and Homeostatic (P2ry12, Cd33, Tmem119, Csf1r, Cx3cr1) microglia using snRNAseq data of microglia subcluster 1 from AD mice DG. Gene signature = sum of normalized gene expression for all genes of the gene signature per cell (n = 150 and 229 cells for ‘Sed’ and ‘Run’, respectively). Two-tailed Mann Whitney, DAM P = 0.0195 and Homeostatic P = 0.9858. h, Bar plots of gene signatures for DAM (Irf8, Trem2, Igf1, Axl, and Csf1) and Homeostatic microglia (P2ry12, Cd33, Tmem119, Csf1r, Cx3cr1) in isolated CD11b+ cells (microglia) from the cortex and hippocampus of the 5xFAD mouse model using QPCR. Gene signature = sum of normalized gene expression for all genes of the gene signature per animal (n = 8 and 7 for ‘Sed’ and ‘Run’, respectively). Two-tailed unpaired t-test, DAM P = 0.0616 and Homeostatic P = 0.9462. Data represented by the mean ± s.e.m. (a, b, d, h) or by the median (middle bold line) and upper and lower quartiles (lighter dotted lines) (g) of biologically independent samples.

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