title: A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells.
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 alpha, 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/beta-catenin-related genes downregulated, and the translocation of beta-catenin was observed along the cell membrane and in the cytoplasm, although some beta-catenin was still in the nucleus. Downregulation of Wnt/beta-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 beta-catenin was similar to that of cells treated with 5-azacytidine/HGF/OSM/FGF2. In conclusion, the suppression of Wnt/beta-catenin signaling induced the hepatic differentiation of UCBMSCs, suggesting that Wnt/beta-catenin signals play an important role in the hepatic fate specification of human UCBMSCs.
authors: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
authors: Yoko
authors: Y
authors: Yoshida
authors: Takashi
authors: T
authors: Shimomura
authors: Tomohiko
authors: T
authors: Sakabe
authors: Kyoko
authors: K
authors: Ishii
authors: Kazue
authors: K
authors: Gonda
authors: Saori
authors: S
authors: Matsuoka
authors: Yumi
authors: Y
authors: Watanabe
authors: Kazuko
authors: K
authors: Takubo
authors: Hiroyuki
authors: H
authors: Tsuchiya
authors: Yoshiko
authors: Y
authors: Hoshikawa
authors: Akihiro
authors: A
authors: Kurimasa
authors: Ichiro
authors: I
authors: Hisatome
authors: Taro
authors: T
authors: Uyama
authors: Masanori
authors: M
authors: Terai
authors: Akihiro
authors: A
authors: Umezawa
authors: Goshi
authors: G
authors: Shiota
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D005312:Fetal Blood / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000166:cytology* / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014508:Urea / Q000032:analysis; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D017931:DNA Primers; D051153:Wnt Proteins; D051176:beta Catenin; D014508:Urea