Extended Data Fig. 5. Hepatocytes and cholangiocytes are strongly affected by disease progression.

a) GSEA analysis of hepatocytes across disease stages. Examples of significantly enriched terms are shown for each disease stage. Benjamini-Hochberg corrected values shown. b) Statistical analysis corresponding to Fig. 3b. Expression-based correlations for pericentral and periportal genes, compared within groups (pericentral vs pericentral and periportal vs periportal) or between groups (pericentral vs periportal) across disease stages. P-values corresponding to comparisons of distributions for within-group and between-group correlations are indicated. Statistical significance was calculated using two-sided Welch’s t-test. Per disease stage n = 66 pairwise correlations between unique pairs of genes were compared (Pericentral_Pericentral: 15, Pericentral_Periportal: 36, Periportal_Periportal: 15). Mid-point, minimum and maximum of the boxplot summary correspond to the median, first and third quartiles. The extent of the whiskers correspond to the largest/smallest value no further than 1.5*IQR from the inter-quartile range. Points beyond this range are defined as outliers and are plotted individually. c) FLASH imaging of cleared healthy and end-stage liver tissue, with staining for pan-hepatocyte marker GSTA1 and pericentral hepatocyte marker GLUL. In healthy the high magnification (yellow box and right panel) highlights a region of the central vein with a view displayed through the lumen of the vessel. In end-stage the high magnification examines one side of a hepatocyte nodule. See also supplementary videos 1 and 2. Scale bars = 400 um low magnifications and 200 um high magnifications (right panels). d) FLASH imaging of highlighting ductal endings in healthy and end stage samples. Yellow arrows indicate single cell endings in healthy and bulkier endings in end stage samples. Scale bars = 50 um. n = 3 healthy and 3 end stage patient tissue samples (c-d).