Extended Data Fig. 7: Despite the increased morphology-based senescence index, 3xDR microglia do not display a senescent state at the transcriptional level.
From: Transcriptional and epigenetic decoding of the microglial aging process
(a) Volcano plots of DEGs in 3xDR vs. control microglial transcriptomes (log2 FC > 0.25, adjusted P value < 0.05). Non-parametric Wilcoxon rank sum test. (b) Top 10 significantly enriched biological processes (Q < 0.05) in 3xDR vs. control microglia. The orange bar represents up-regulated gene-enriched pathways; the blue bar represents down-regulated gene-enriched pathways. (c) UMAP plot of LPS-treated, PBS-treated and 3xDR microglia, revealing that 3xDR microglia do not exhibit a reactive phenotype. (d) Senescence index of microglia in the control and forced turnover groups, calculated as the area of IBA1 (mm2) divided by the area under the curve (AUC). Data are represented as the mean ± SD. N = 8 and 7 mice for control and 3xDR, respectively. Two-tailed independent t test. (e) Quantification of β-gal levels in cortical and hippocampal microglia. IBA1 area, β-gal area or β-gal+ microglia are not changed in 3xDR mice. Data are presented as mean ± SD. N = 9 mice for each group, 60 cells in total. Two-tailed independent t test. (f) Scatter plot showing the correlation between well-known senescence genes and the 3xDR microglial phenotype, indicating that well-defined senescence genes are not correlated with 3xDR microglia. Pearson correlation. (g) 3xDR and control microglia exhibit similar SASP gene signature scores. PLX5622: PLX5622-formulated diet; CD: control diet; Ctrl: control; 3xDR: 3-round depletion-repopulation; FC: fold change; SASP: senescence-associated secretory phenotype; FOV: field of view; AU: arbitrary unit.
