title: 5-azacytidine promotes the transdifferentiation of cardiac cells to skeletal myocytes.
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.
authors.affiliation: New York Medical College/Westchester Medical Center Stem Cell Laboratory, Departments of Physiology and Medicine, New York Medical College , Valhalla, NY, 10595.
authors.forename: Keerat
authors.initials: K
authors.lastname: Kaur
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yang
authors.forename: Carol A
authors.initials: CA
authors.lastname: Eisenberg
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Eisenberg
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001374:Azacitidine