Fig. 2From: Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s diseaseDecreases in gene expression linked to homeostatic microglia in mouse models of neurodegenerative diseases. Expression of homeostatic microglial genes analyzed by RNA sequencing (RNA-seq) and quantitative PCR (WT: n = 4 and AppNL-G-F/NL-G-F: n = 4; Ctrl: n = 3 and rTg4510: n = 3; WT: n = 4 and SOD1G93A: n = 4). WT, wild-type; Ctrl, control. a A heat map of homeostatic microglial genes in isolated-microglia of the mouse models of neurodegenerative diseases. Colors of the individual cells denote relative expression levels of the neurodegenerative models. +: q < 0.05, ++: q < 0.001. b, c Quantitative PCR analysis to determine the expression levels of P2ry12 and Sall1 mRNA in isolated-microglia of each mouse model. b P2ry12 expression level (AppNL-G-F/NL-G-F: FC = −1.14, p = 0.2275; rTg4510: FC = −2.07, p = 0.00285; SOD1G93A: FC = −7.35, p = 1.74E−06). c Sall1 expression level (AppNL-G-F/NL-G-F: FC = −1.02, p = 1; rTg4510: FC = −2.21, p = 0.0420; SOD1G93A: FC = −4.04, p = 6.71E−05). Data are represented as the mean ± SEM. *p < 0.05, **p < 0.001. Bonferroni-corrected Student’s t test. d Log2FC values against WT/Ctrl for 68 homeostatic microglial genes in the isolated microglia from the cortex of APPNL-G-F/NL-G-F and rTg4510 mice, and spinal cord of SOD1G93A mice. AppNL-G-F/NL-G-F (median log2FC = 0.227), rTg4510 (median log2FC = −0.0504, adj. p = 7.33E−07), and SOD1G93A (median log2FC = −0.633, adj. p = 1.61E−11) mice. Data are represented as the median with 5th and 95th percentile. *p < 0.05, **p < 0.001. Wilcoxon’s signed rank test, followed by a multiple testing correction using the Bonferroni–Holm method. e–g Representative immunofluorescent images demonstrating amyloid β (Aβ, thioflavin), Tau (AT8) or hSOD1 (white), Iba1 (green), and TMEM119 (red) in cortex of e WT and AppNL-G-F/NL-G-F mouse, f Ctrl and rTg4510 mouse, and g spinal cord of WT and SOD1G93A mouse. Arrowheads indicate Aβ and Aβ-associated microglia. Scale bars: 20 µm (e, f) and 50 µm (g)Back to article page