Extended Data Fig. 10: Characterization of the cellular interactome in the fibrotic niche.

a, b, Representative immunofluorescence images (n ≥ 3) of fibrotic niche in cirrhotic liver. a, TREM2 (red), PLVAP (white), PDGFRα (green) and DAPI (blue). b, TREM2 (red), ACKR1 (white), PDGFRα (green) and DAPI (blue). c, Proliferation assay. Human HSCs were treated with conditioned medium from primary hepatic macrophage subpopulations SAMac (n = 2), TMs (n = 2), KCs (n = 2) or control medium (n = 2). The AUC of the percentage change in HSC number over time (hours) is shown on the y axis. Data are mean ± s.e.m. d, Circle plot showing potential interaction magnitude from ligands expressed by SAMacs and SAEndos to receptors expressed on SAMes. e, Circle plot showing potential interaction magnitude from ligands expressed by SAMes to receptors expressed on SAMacs and SAEndos. f, Dot plot of ligand–receptor interactions between SAMes (n = 7 human livers), SAMacs (n = 10 human livers) and SAEndos (n = 7 human livers). Ligand (red) and cognate receptor (blue) shown on the x axis; populations that express ligand (red) and receptor (blue) are shown on the y axis; circle size denotes P value (permutation test); colour (red, high; yellow, low) denotes average ligand and receptor expression levels in interacting subpopulations. g, Top, representative immunofluorescence image (n ≥ 3) of CCL2 (red), CCR2 (white), PDGFRα (green) and DAPI (blue) in fibrotic niche in cirrhotic liver; arrows denote CCL2⁺PDGFRα⁺ cells. Bottom, representative immunofluorescence image (n ≥ 3) of ANGPT1 (red), TEK (white), PDGFRα (green) and DAPI (blue) in fibrotic niche in cirrhotic liver; arrows denote ANGPT1⁺PDGFRα⁺ cells. h, Circle plot denotes potential interaction magnitude from ligands expressed by SAMacs to receptors expressed on SAEndos. i, Dot plot of ligand–receptor interactions between SAMacs (n = 10 human livers) and SAEndos (n = 7 human livers) as in f. j, Representative immunofluorescence image (n ≥ 3) of TREM2 (red), FLT1 (white), VEGFA (green) and DAPI (blue) in fibrotic niche in cirrhotic liver; arrows denote TREM2⁺VEGFA⁺ cells. k, Circle plot of the potential interaction magnitude from ligands expressed by SAEndos to receptors expressed on SAMacs. l, Dot plot of ligand–receptor interactions between SAEndo (n = 7 human livers) and SAMacs (n = 10 human livers) as in f. m, Top, representative immunofluorescence image (n ≥ 3) of TREM2 (red), CD200 (white), CD200R (green) and DAPI (blue) in fibrotic niche in cirrhotic liver; arrows denote TREM2⁺CD200R⁺ cells. Bottom, representative immunofluorescence image (n ≥ 3) of TREM2 (red), DLL4 (white), NOTCH2 (green) and DAPI (blue) in fibrotic niche in cirrhotic liver; arrows denote TREM2⁺NOTCH2⁺ cells. All scale bars, 50 μm.

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