Fig. 5: Late DNA methylation inhibition represses BPPC redifferentiation through p53 activation.

a Experimental scheme illustrating the 5azaC and Mtz treatment and analysis from R8h to R48h. b Bisulfite sequencing analysis of DNA methylation at the p53 locus in DNA isolated from DMSO and 5azaC-treated livers. c WISH images showing the expression of p53 from R8h to R48h during liver regeneration after late DNA methylation inhibition. Quantification of the intensity of p53 expression in liver regions from R8h to R48h. d Experimental scheme illustrating the 5azaC and Mtz treatment and analysis at R48h in p53 mutant and WT. e Single-optical section images showing the expressions of hepatocyte marker Bhmt and BECs marker Alcam at R48h. Quantification of the intensity of Bhmt expression and the percentage of Alcam+ among Dendra2+ cells in liver regions at R48h. f WISH images showing the expressions of cp and gc at R48h after 5azaC treatment in control and p53 mutant after late DNA methylation inhibition. Quantification of the intensity of cp and gc expressions in liver regions at R48h. Note that the downregulation of cp and gc expressions was recovered in p53 mutant after 5azaC treatment. Asterisks indicate statistical significance: ***P < 0.001; ****P < 0.0001 using t-tests analysis when compared to control. Scale bars: 100 µm; error bars, ±SEM. DAPI 4′,6-diamidino-2-phenylindole, BT before treatment, ns no significant difference, R regeneration time after the withdrawal of Mtz.