Fig. 8: TREM2+ scar-associated macrophages express a human MSen gene signature.
a, Illustration of the in vitro model system using exogenous DNA damage with irradiation and Doxo on PBMC-derived macrophages from male and female human donors. b, Mean ± s.e. gene expression (RT–qPCR) normalized to control. n = 9 donors (mixed male and female) for control and Sen(IR) conditions. n = 8 for Sen(Doxo) conditions. P value from Tukey’s test post repeated measures ANOVA analysis. c, SDS–PAGE gels and immunostaining (western blot) for p21 and p16 in response to 10 days post DNA damage. ImageJ quantification for band intensity is shown to the right and represents relative intensity over the loading control. d, SA-β-gal images of human senescent macrophages. e, Click-iT EdU labeling of cells to assess proliferation dynamics. Axes represent the percentage of cells positive for the stain relative to the parental gate, as detected by flow cytometry. The bar plot represents the mean ± s.e. of n = 3 independent donors. P value derived from unpaired one-sided t-test. f, PCA on bulk RNA-seq samples from 10 days post DNA damage for three blood donors. g, Heatmap projection of all statistically significant DEGs compared to control conditions. h, KEGG pathway enrichment analysis for the top ten pathways downregulated in human senescent macrophages. i, KEGG pathway enrichment analysis for the top ten pathways upregulated in human senescent macrophages. j, Model illustration of running MSen score on publicly accessible single-cell dataset49 of human liver biopsy samples from five people with liver cirrhosis and five with a healthy liver. k, UMAP projection of all annotated CD45+ cell types and colored by human MSen Seurat score. l, UMAP projection of CD68+ cells (macrophages) in healthy and cirrhotic tissue samples. Color denotes human MSen Seurat score. m, Distribution of MSen Seurat score across resident macrophage (Kupffer cells) and non-resident monocyte and macrophage populations in healthy and cirrhotic conditions. P value represents the results of a two-sided t-test. n, Distribution of human MSen score across all CD45+ cell types in the dataset. ALD, alcohol-related liver disease; F, female; KC, Kupffer cell; IgA, immunoglobulin A; IL-C, innate lymphoid cell; M, male; MoMac, monocyte-derived macrophage; Mø, macrophage; PBC, primary biliary cholangitis; pDC, plasmacytoid dendritic cell. Panels a and j created in BioRender; Salladay-Perez, I. https://biorender.com/6umuckd (2026).
