Modulation of reversibility by DNA Methyltransferases during hepatogenic differentiation in Mesenchymal Stromal Cells

Accession Number: GSE73617

Platform:
GPL1261: [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

Organism: Mus musculus

Published on 2017-08-11

Summary:
Mesenchymal stromal cells (MSCs) hold great promise in the field of liver regenerative medicine. However, the mechanisms and reversibility of hepatogenic differentiation in MSCs are poorly understood. Here, we demonstrate that hepatogenic differentiation of MSCs is a reversible process and is modulated by the transforming growth factor beta 1- DNA methyltransferases (TGF-β1-Dnmts) axis. Dnmt1 and Dnmt3a differentially regulate hepatogenic differentiation and de-differentiation in response to the alternation of TGF-β1 concentration. Knockdown of Dnmt1 accelerates the hepatogenic differentiation in MSCs-derived hepatocyte-like cells (dHeps) whereas Knockdown of Dnmt3a represses hepatogenic differentiation. Conclusions: Our finding first demonstrates that epigenetic regulation by Dnmts in response to stimulation from the surrounding microenvironment controls the reversibility of hepatogenic differentiation in MSCs. Manipulation of Dnmts provides a rapid and efficient differentiation protocol to generate functional dHeps from MSCs that may provide clinical potential for regenerative medicine.

Overall Design:
Gene expression analysis of hepatogenic differentiation: MSC samples, HD28 samples, dHD28 samples, MLC samples and Hepatocyte samples.

Contact:
Name: Chien-Wei Lee
Organization: National Yang-Ming University
Address: No.155, Sec.2, Linong Street Taipei Taiwan
Email: [email protected]

Organization: Affymetrix, Inc.
Address: Santa Clara CA 95051 USA
Email: [email protected], [email protected]
Phone: 888-362-2447
Web-Link: http://www.affymetrix.com/index.affx