Panel A shows flow cytometry plots and bar graphs comparing phagocytic receptor expression in liver and blood monocytes/macrophages in a PSC patient and a non-PSC control. Panel B shows a UMAP plot clustering Kupffer cells (KCs), macrophages, and monocytes from single-cell sequencing datasets. Panel C shows violin plots comparing normalized phagocytic signature expression across immune-cell populations and disease conditions. Panel D shows UMAP feature plots displaying ALB, APOA1, and CYP3A4 expression across immune-cell populations. Panel E shows a violin plot comparing phagocytic signature expression in KCs expressing or not expressing hepatocyte messenger RNA (KCs-Hep mRNA pos and KCs-Hep mRNA neg). Panel F shows a waterfall bar graph comparing phagocytosis-associated and liver X receptor-dependent gene expression changes in KCs expressing or not expressing hepatocyte messenger RNA. Panel G shows a waterfall bar graph comparing phagosome-maturation-associated gene expression changes between KC groups.
Kupffer cells from PSC patients show enrichment in hepatocyte transcripts and reduced phagocytic signature. (A) FACS plots reporting gating strategy for analysis of CD66b−CD68+CD14+CCR2+ and CD66b−CD68+CD14+CCR2− Mφ/monocytes isolated from the liver and the blood of a PSC patient and a non-PSC patient control (Control). Bar graph reporting the frequency of cells expressing different efferocytic/scavenger receptors is shown. n = 1 patient/condition. (B) UMAP of Kupffer cells (KCs), Mφ, and monocytes from scRNAseq data from Andrews et al. (2024) of six normal (control), two PBC, and eight PSC livers. (C) Normalized expression score of phagocytic gene signature for different cell types across conditions. The horizontal bar of violin plot indicates the median. P value indicates Wilcoxon signed-rank test. (D) Normalized gene expression of selected genes on UMAP from B. (E) Normalized expression score of phagocytic gene signature for KCs from PSC patients either expressing (KCs-Hep mRNA pos) or not (KCs-Hep mRNA neg) hepatocyte-associated mRNA (ALB, APOA1, and CYP3A4). The horizontal bar of violin plot indicates the median. P value indicates Wilcoxon signed-rank test. (F and G) Waterfall plots displaying the log2 fold change (Log2FC) in expression of (F) phagocytosis-associated and LXR-dependent genes and (G) phagosome maturation-associated genes in KCs-Hep mRNA pos compared with KCs-Hep mRNA neg from PSC patients. *P < 0.05; ****P < 0.0001.