NYMC Faculty Publications

5-azacytidine Promotes the Transdifferentiation of Cardiac Cells to Skeletal Myocyte

Author Type(s)

Faculty

DOI

10.1089/cell.2014.0021

Journal Title

Cell Reprogram

First Page

324

Last Page

330

Document Type

Article

Publication Date

10-1-2014

Department

Biochemistry and Molecular Biology

Keywords

Animals, Azacitidine, Cell Line, Cell Transdifferentiation, Mice, Mice, Inbred BALB C, Muscle, Skeletal, Myocardium, Reverse Transcriptase Polymerase Chain Reaction

Disciplines

Medicine and Health Sciences

Abstract

The DNA methylation inhibitor 5-azacytidine is widely used to stimulate the cardiac differentiation of stem cells. However, 5-azacytidine has long been employed as a tool for stimulating skeletal myogenesis. Yet, it is unclear whether the ability of 5-azacytidine to promote both cardiac and skeletal myogenesis is dependent strictly on the native potential of the starting cell population or if this drug is a transdifferentiation agent. To address this issue, we examined the effect of 5-azacytidine on cultures of adult mouse atrial tissue, which contains cardiac but not skeletal muscle progenitors. Exposure to 5-azacytidine caused atrial cells to elongate and increased the presence of fat globules within the cultures. 5-Azacytidine also induced expression of the skeletal myogenic transcription factors MyoD and myogenin. 5-Azacytidine pretreatments allowed atrial cells to undergo adipogenesis or skeletal myogenesis when subsequently cultured with either insulin and dexamethasone or low-serum media, respectively. The presence of skeletal myocytes in atrial cultures was indicated by dual staining for myogenin and sarcomeric α-actin. These data demonstrate that 5-azacytidine converts cardiac cells to noncardiac cell types and suggests that this drug has a compromised efficacy as a cardiac differentiation factor.

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