A role of Wnt/β-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells

Authors:
  • TSTakashi Shimomura
    Takashi Shimomura
  • TSTomohiko Sakabe
    Tomohiko Sakabe
  • KIKyoko Ishii
    Kyoko Ishii
  • KGKazue Gonda
    Kazue Gonda
  • SMSaori Matsuoka
    Saori Matsuoka
  • YWYumi Watanabe
    Yumi Watanabe
  • KTKazuko Takubo
    Kazuko Takubo
  • HTHiroyuki Tsuchiya
    Hiroyuki Tsuchiya
  • YHYoshiko Hoshikawa
    Yoshiko Hoshikawa
  • AKAkihiro Kurimasa
    Akihiro Kurimasa
  • IHIchiro Hisatome
    Ichiro Hisatome
Publisher website
Google Scholar
Abstract
Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to be an excellent source of cells for transplantation. In addition, the stem cell plasticity of human UCBMSCs, which can transdifferentiate into hepatocytes, has been reported. However, the mechanisms involved remain to be clarified. To identify the genes and/or signals that are important in specifying the hepatic fate of human UCBMSCs, we analyzed gene expression profiles during the hepatic differentiation of UCBMSCs with human telomerase reverse transcriptase, UCBMSCs immortalized by infection with a retrovirus carrying telomerase reverse transcriptase, but whose differentiation potential remains unchanged. Efficient differentiation was induced by 5-azacytidine (5-aza)/hepatocyte growth factor (HGF)/oncostatin M (OSM)/fibroblast growth factor 2 (FGF2) treatment in terms of function as well as protein expression: 2.5-fold increase in albumin, 4-fold increase in CCAAT enhancer-binding protein α, 1.5-fold increase in cytochrome p450 1A1/2, and 8-fold increase in periodic acid-Schiff staining. Consequently, we found that the expression of Wnt/β-catenin-related genes downregulated, and the translocation of β-catenin was observed along the cell membrane and in the cytoplasm, although some β-catenin was still in the nucleus. Downregulation of Wnt/β-catenin signals in the cells by Fz8-small interference RNA treatment, which was analyzed with a Tcf4 promoter-luciferase assay, resulted in similar hepatic differentiation to that observed with 5-azacytidine/HGF/OSM/FGF2. In addition, the subcellular distribution of β-catenin was similar to that of cells treated with 5-azacytidine/HGF/OSM/FGF2. In conclusion, the suppression of Wnt/β-catenin signaling induced the hepatic differentiation of UCBMSCs, suggesting that Wnt/β-catenin signals play an important role in the hepatic fate specification of human UCBMSCs.

This publication has 47 references indexed in Scilit: