Fig. 2: HSCs regulate metabolic zonation and zone-specific injury and proliferation in the liver.
From: Hepatic stellate cells control liver zonation, size and functions via R-spondin 3
a,b, The top 40 genes downregulated in RNA-seq data from HSC-depleted mice versus controls (ctrl) in the iDTR × Lrat-cre and the JEDI models versus controls after subtraction of HSC-enriched genes (a), and qPCR confirmation in iDTRWT (n = 8) and iDTRhet (n = 11) mice (b) of select genes in livers from the iDTR × Lrat-cre model. c, CYP2E1, CYP1A2 and CYP2F2 IHC and quantification in iDTRWT (n = 8) and iDTRhet (n = 8) mice 7 days after treatment with diphtheria toxin. c, central vein; p, portal vein. d, Multiplex IHC analysis showing significantly altered expression of zonal genes in iDTRWT (n = 5) and iDTRhet (n = 5) mice. e, Zonal quantification of the indicated zone 1 (Zo1), zones 2–3 and strictly zone 3 markers from IHC performed in Fig. 2c and Extended Data Fig. 4g in iDTRWT and iDTRhet mice (n = 8 per group). f, 100-plex spatial transcriptomics for WNT-regulatory, WNT-target and cell marker genes shows differences in zonation patterns and WNT-target genes between iDTRWT (n = 1) versus iDTRhet (n = 1) mice. g,h, Zonal quantification of Ki-67+ cells after 70% PHx and TCPOBOP treatment (g) or of necrosis after APAP, CCl4 or allyl alcohol treatment (h) in iDTRWT (n = 5–8) and iDTRhet (n = 4–11) mice. Data are mean ± s.e.m. For b and c, each dot represents one biological replicate. Scale bars, 100 µm (c and d) and 1 mm (f). P values were calculated using unpaired two-tailed t-tests (b, c, e, g and h). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. AU, arbitrary units.
