Extended Data Fig. 7: Steatohepatitis and liver fibrosis in Tet2−/− and Dnmt3a−/− transplanted mice.
From: Clonal haematopoiesis and risk of chronic liver disease
a, Selected gene signatures enriched in bulk liver transcripts from Tet2−/− (n = 4) transplanted mice fed CDAHFD relative to control vavCre+ (wt; n = 4) transplanted mice. b, Histologic features of steatohepatitis in Ldlr−/− mice transplanted with Tet2−/− (n = 27) and control vavCre+ (wt; n = 30) bone marrow and fed Western diet for 10 weeks were graded on a semiquantitative scale and aggregated into a NASH activity score (NAS) using CRN histologic scoring criteria. c-f, Graded histologic features included steatosis (c), inflammatory foci (d), hepatocyte ballooning (e, arrowhead) and apoptosis (f, arrow). g, Masson’s trichrome staining demonstrates absence of perivenular fibrosis in control and Tet2−/− transplanted mice. h, B6.SJL mice were transplanted with Dnmt3a−/− (n = 24) or control vavCre+ (wt; n = 20) bone marrow cells and fed CDAHFD for 11 weeks. Steatohepatitis was assessed histologically for steatosis, inflammation, and hepatocyte ballooning. Collagen fibrosis was measured by Masson’s trichrome staining. i, B6.SJL mice were transplanted with Tet2−/− (n = 20) or control vavCre+ (wt; n = 15) bone marrow cells and fed CDAHFD for 11 weeks, then reverted to standard chow for 10 days. Compared to control animals, Tet2−/− transplanted mice show similar resolution of liver fat but show persistently greater inflammation and more hepatocyte ballooning. Collagen fibrosis, as measured by Masson’s trichrome staining, was not significantly different. Data from one (a) or two independent experiments (b, h, i) are shown. NES, normalized enrichment score; FDR, false discovery rate.
