Valproic acid promotes differentiation of hepatocyte-like cells from whole human umbilical cord-derived mesenchymal stem cells

Su Yeon An, Jiyou Han, Hee Joung Lim, Seo Young Park, Ji Hyang Kim, Byung Rok Do, Jong Hoon Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) are mesoderm-derived cells that are considered a good source of somatic cells for treatment of many degenerative diseases. Previous studies have reported the differentiation of mesodermal MSCs into endodermal and ectodermal cell types beyond their embryonic lineages, including hepatocytes and neurons. However, the molecular pathways responsible for the direct or indirect cell type conversion and the functional ability of the differentiated cells remain unclear and need further research. In the present study, we demonstrated that valproic acid (VPA), which is a histone deacetylase inhibitor, induced an increase in the expression of endodermal genes including CXCR4, SOX17, FOXA1, FOXA2, GSC, c-MET, EOMES, and HNF-1β in human umbilical cord derived MSCs (hUCMSCs). In addition, we found that VPA is able to increase these endodermal genes in hUCMSCs by activating signal transduction of AKT and ERK. VPA pretreatment increased hepatic differentiation at the expense of adipogenic differentiation. The effects of VPA on modulating hUCMSCs fate were diminished by blocking AKT and ERK activation using specific signaling inhibitors. Together, our results suggest that VPA contributes to the lineage conversion of hUCMSCs to hepatic cell fate by upregulating the expression of endodermal genes through AKT and ERK activation.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalTissue and Cell
Volume46
Issue number2
DOIs
Publication statusPublished - 2014 Apr

Keywords

  • AKT
  • Differentiation
  • ERK
  • Endoderm
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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