Extended Data Fig. 12: HGF deletion in HSC promotes fibrosis and inflammation in CCl4-induced liver injury.
From: Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis
a–c, UMAP visualization of Hgf and/or Met in the 8xCCl4 injured (n = 3 mice) (a) or normal mouse livers (n = 1) by scRNAseq (c) and in the human normal (n = 4 cases), cirrhotic (n = 4 cases) and HCC (n = 2 cases) livers by snRNAseq (b). d, significant reduction of Hgf mRNA in normal (n = 4 mice/group) and CCl4 liver (Untreated (UT): n = 3 mice, Hgf fl/fl: n = 8 mice, Hgf ΔHSC: n = 7 mice) as well as of HGF protein in livers (UT: n = 4 mice, CCl4: n = 5 mice/group) e, Fibrosis was assessed by Sirius Red staining in the non-tumour tissue from Hgf ΔHSC mice (n = 10 mice) compared to Hgf f/f littermates (n = 11 mice) during HCC development induced by DEN (i.p. 25 mg/kg at 2 weeks old) followed by 12 injections of CCl4 (i.p. 0.5 µL/g, 1x/week)4. f, HSC activation was determined by qPCR for the fibrogenic genes Col1a1 and Lox in livers from Hgf ΔHSC (n = 4 mice) and Hgf f/f mice (n = 7 mice) treated with injections of 6xCCl4. g, flow cytometric analysis of CD45+ cells as well as myeloid and lymphocyte populations in livers from Hgf ΔHSC (n = 7 mice) compared to Hgf f/f mice (n = 8 mice) treated with injections of 6xCCl4. h, qPCR for inflammatory genes from Hgf ΔHSC (n = 7 mice) and Hgf f/f (n = 8 mice) livers after treatment with 6xCCl4 injections. i, Liver/body ratio (LBR) in Hgf fl/fl (Ctrl: n = 10 mice, pHx: n = 6 mice) and Hgf ΔHSC (Ctrl: n = 8 mice, pHx: n = 7 mice) mice in untreated mice or after 48h partial hepatectomy (pHx) (left panel). Hepatocyte proliferation assessed by Ki67 staining 48h after PHx (right panel - Hgf f/f: n = 6 mice, Hgf ΔHSC: n = 7 mice). Data are shown as mean ± SEM, each data point represents one cell (a-c) or one individual (d-i), scale bars: 200 µm. GZB, granzyme B. Statistics: Data in d-g and i were analysed by two-tailed Student’s t-test. Data in h were analysed by two-tailed Mann-Whitney test. Raw data are given in Source Data and gating strategy for g in Supplementary Fig. 5
