title: Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes.
abstract: Recent advances in the direct conversion of fibroblasts to cardiomyocytes suggest this process as a novel promising approach for cardiac cell-based therapies. Here, by screening the effects of 10 candidate small molecules along with transient overexpression of Yamanaka factors, we show ascorbic acid (AA), also known as vitamin C, enhances reprogramming of mouse fibroblasts into beating cardiomyocytes. Immunostaining and gene expression analyses for pluripotency and cardiac lineage markers confirmed beating patches were derived from non-cardiac lineage cells without passing through a pluripotent intermediate. Further analysis revealed that AA also increased the size of the beating areas and the number of cardiac progenitors. Immunostaining for cardiac markers, as well as electrophysiological analysis confirmed the functionality of directly converted cardiomyocytes. These results illustrate the importance of AA in direct conversion of fibroblasts to cardiomyocytes and may open new insights into future biomedical applications for induced cardiomyocytes.
authors.affiliation: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Talkhabi
authors.affiliation: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Pahlavan
authors.affiliation: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: Nasser.Aghdami@RoyanInstitute.org.
authors.forename: Nasser
authors.initials: N
authors.lastname: Aghdami
authors.affiliation: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran. Electronic address: Baharvand@RoyanInstitute.org.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*
chemical_list: D001205:Ascorbic Acid
keywords: Ascorbic acid; Cardiomyocytes; Direct conversion; Fibroblasts; Small molecules