DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells

Chien-Wei Lee, Wei-Chih Huang, Hsien-Da Huang, Yi-Hsiang Huang, Jennifer H. Ho, Muh-Hwa Yang, Vincent W Yang, Oscar K. Lee

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor beta 1 (TGF beta 1), which in turn controls hepatogenic differentiation and de-differentiation. In addition, a stepwise reduction in TGF beta 1 concentrations in culture media increases DNMT1 and decreases DNMT3 in primary hepatocytes (Heps) and confers Heps with multi-differentiation potentials similarly to MSCs. Hepatic lineage reversibility of MSCs and lineage conversion of Heps are regulated byDNMTs in response to TGF gamma 1. This previously unrecognized TGF beta 1-DNMTs-MSC-HD axis may further increase the understanding the normal and pathological processes in the liver, as well as functions of MSCs after transplantation to treat liver diseases.
Original languageEnglish
Pages (from-to)247-263
Number of pages7
JournalStem Cell Reports
Volume9
DOIs
StatePublished - 11 Jul 2017

Keywords

  • STEM-CELLS; PROGENITOR CELLS; MOUSE-LIVER; MALIGNANT-TRANSFORMATION; CHROMOSOMAL INSTABILITY; STEM/PROGENITOR CELLS; MATURE HEPATOCYTES; IN-VITRO; REGENERATION; CULTURE

Fingerprint Dive into the research topics of 'DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells'. Together they form a unique fingerprint.

Cite this