Extended Data Fig. 2: Circadian clock disruption limits hepatocyte proliferation after resection.

a,b, Representative IHC images (a) and quantification (b) of Ki67-positive staining cells in AL, DRF and LBKO mice with sham- or PH- operation. More than three fields for each of three independent samples were counted. Scale bar, 100 μm. c-g, Graphs showing the expression of Bmal1 (c), the liver-body weight ratio (d), the contents of ALT (e) and AST (f), and representative IHC images and quantification of Ki-67 staining (g) in the livers on day 4 post-PH. Male adult Bmal1f/f mice were infected with control AAV8 (AAV-NC) or AAV8-TbgCre (AAV-Cre) and then subjected to PH. Five fields for each of three independent samples were counted. Scale bar, 100 μm. h-j, Graphs showing the liver-body weight ratio (h) and the contents of ALT (i) and AST (j) in mice which fed with DRF for 10 days were then subjected to PH. The samples were collected on day 4 post-PH. The red line indicates the mean value of DRF-D4 group. k, qPCR analysis showing the pattern of Pcna mRNA expression in the livers of WT, LBKO and DRF mice at various ZTs. For c,k, n = 3 mice per group. For d-f,h-j, n = 5 mice per group. Data are mean ± s.e.m. P-values were calculated using one-way ANOVA with Dunnett’s test (b) and unpaired two-tailed Student’s t-test (c-j). For k, JTK_CYCLE was applied to determine rhythmicity. P < 0.05 was considered to be rhythmic.