Fig 1: Multi-lineage interactions in the fibrotic niche.a, Dotplot: ligand-receptor interactions between SAMF (n=10 human livers) and SAMes (n=7 human livers). X-axis, ligand (red) and cognate receptor (blue); y-axis, cell populations expressing ligand (red) and receptor (blue); circle size, P value (permutation test); colour (red, high; yellow, low), means of average ligand and receptor expression levels in interacting subpopulations. b, Representative immunofluorescence images, fibrotic niche. Left, TREM2 (red), PDGFB (white), PDGFRa (green), DAPI (blue), arrows TREM2+PDGFB+ cells. Right, TNFRSF12A (red), TNFSF12 (white), PDGFRa (green), DAPI (blue), arrows TNFRSF12A+PDGFRa+ cells, scale bars 50µm. c to d, HSC proliferation assay: y-axis, area under curve (AUC) of % change in HSC number over time (hours), Mean±SEM, one-way ANOVA and Tukey. c, Control, TNFSF12, anti-TNFRSF12A, isotype control, all n=3. d, Vehicle, PDGF-BB, Crenolanib, all n=3. e, Dotplot: ligand-receptor interactions between SAEndo (n=7 human livers) and SAMes (n=7 human livers). X-axis, ligand (red) and cognate receptor (blue); y-axis, cell populations expressing ligand (red) and receptor (blue); circle size, P value (permutation test); colour (red, high; yellow, low), means of average ligand and receptor expression levels in interacting subpopulations. f, Representative immunofluorescence image, fibrotic niche. NOTCH3 (red), DLL4 (white), PDGFRa (green), DAPI (blue), arrows NOTCH3+PDGFRa+ cells, scale bar 50µm. g, Endothelial cell JAG1 flow cytometry: healthy (n=3) or cirrhotic (n=9) liver, representative histogram (left), mean fluorescence intensity (MFI, right), Mean±SEM, Mann-Whitney two-tailed. h, Cirrhotic endothelial cell and HSC co-culture, Notch inhibitor Dibenzazepine (DBZ). Representative immunofluorescence images (left), Collagen 1 (magenta), PECAM1 (green), DAPI (blue). Digital pixel analysis (right); collagen 1 area, n=3, Mean±SEM, RM one-way ANOVA and Tukey. n, HSC gene knockdown: control (n=7) or NOTCH3 (n=7) siRNA, qPCR of stated gene, expression relative to mean expression of control siRNA, Mean±SEM, Mann-Whitney two-tailed.