title: Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy.
abstract: Here we show that conventional reprogramming towards pluripotency through overexpression of Oct4, Sox2, Klf4 and c-Myc can be shortcut and directed towards cardiogenesis in a fast and efficient manner. With as little as 4 days of transgenic expression of these factors, mouse embryonic fibroblasts (MEFs) can be directly reprogrammed to spontaneously contracting patches of differentiated cardiomyocytes over a period of 11-12 days. Several lines of evidence suggest that a pluripotent intermediate is not involved. Our method represents a unique strategy that allows a transient, plastic developmental state established early in reprogramming to effectively function as a cellular transdifferentiation platform, the use of which could extend beyond cardiogenesis. Our study has potentially wide-ranging implications for induced pluripotent stem cell (iPSC)-factor-based reprogramming and broadens the existing paradigm.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jem A
authors.initials: JA
authors.lastname: Efe
authors.forename: Simon
authors.initials: S
authors.lastname: Hilcove
authors.forename: Janghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Kunfu
authors.initials: K
authors.lastname: Ouyang
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D004594:Electrophysiology / Q000379:methods; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D032383:Myocytes, Cardiac / Q000166:cytology*; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D019076:Transgenes
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D002118:Calcium