Extended Data Fig. 4: FBP1 and TP53 are induced in human MASH and downregulated in daHep.
From: FBP1 controls liver cancer evolution from senescent MASH hepatocytes
a, Relative FBP1 and ALDOB expression from the GSE162694 human normal and MASH liver dataset (normal, n = 31; MASH, 0, n = 35; 1, n = 30; 2, n = 27; 3, n = 8; 4, n = 12). b, Representative IHC of human normal and MASH livers (n = 7-9 BR). Image J quantifications are to the right. c, SR staining and 53BP1 and P-γ-H2AX IHC of human normal and MASH liver tissues (n = 7-9 BR). Image J quantification is shown underneath. d, UMAP visualizations and unsupervised clustering of 78250 hepatocyte nuclei from integrated GSE185477, GSE174748, GSE192742 and GSE212046 datasets. Five hepatocyte subsets were annotated based on gene expression and liver pathology metadata (top left). FBP1 and TP53 expression shown by UMAP visualization (top right and bottom left). NRF2 pathway signatures containing n = 141 target genes in daHep and HCC are shown in the bottom right. The ___location of daHep nuclei is highlighted by blue ellipses. e, UMAP visualizations and unsupervised clustering of 12,540 mouse hepatocyte nuclei from the GSE200366 dataset. Four subsets previously identified, three representing normal hepatocyte zonation (Zone_1_Hep, Zone_2_Hep, Zone_3_Hep) and one daHep cluster. Density maps of Fbp1 and Dnmt1 mRNA expression in the UMAP space are shown with the daHep cluster highlighted by blue ellipses. Data in a, b and c are mean ± SEM. Statistical significance determined by one-way ANOVA with Tukey post-hoc tests or Kruskal–Wallis test with Dunn post-hoc tests (a) and two-sided unpaired t-test or Mann–Whitney U test (b, c) based on data normality distribution. *P < 0.05, **P < 0.01, ****P < 0.0001. Box plots show center line (median), box limits (first and third quartiles) and whiskers (outer data points).
