EZH2 suppresses hepatocellular differentiation of mouse bone marrow mesenchymal stem cells

Our previous studies have indicated that mouse bone marrow mesenchymal stem cells (mBMMSCs) have potential to differentiate into hepatocytes with high efficiency. Our study aimed to evaluate the role of the mouse histone methyltransferase enhancer of zeste homolog 2 gene (EZH2) in the hepatocellular differentiation of mBMMSCs. The mBMMSCs isolated from femurs and tibias were cultured in Iscove's modified Eagle's medium (IMEM) supplemented with 10% fetal bovine serum. Hepatocellular differentiation was induced by 20 ng/mL hepatocyte growth factor and 10 ng/mL fibroblast growth factor 4. The mouse histone methyltransferase EZH2 gene was introduced via PLenti-eGFP-EZH2 or PLenti-eGFP-NEO as a control. Hepatocellular-induced mBMMSCs showed lower expression of EZH2 and lower level of histone H3 lysine 27 trimethylation (H3K27me3) in the AFP and FOXa2 gene promoter regions compared to uninduced mBMMSCs. Introduction of EZH2 inhibited hepatocellular induction, reduced both the mRNA and protein levels of AFP and FOXa2, and increased the level of histone H3K27me3 in the AFP and FOXa2 gene promoter regions. In summary, the mouse histone methyltransferase EZH2 gene could suppress hepatocellular differentiation of mBMMSCs by increasing the level of H3K27me3 in the AFP and FOXa2 gene promoter regions.