title: Combining TGF-β signal inhibition and connexin43 silencing for iPSC induction from mouse cardiomyocytes.
abstract: The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) can be achieved by ectopic expression of defined transcription factors (Oct3/4, Sox2, Klf4 and c-Myc). However, to date, some iPSCs have been generated using viral vectors; thus, unexpected insertional mutagenesis in the target cells would be a potential risk. Here we report reprogramming of siPSCs (gene silencing-induced pluripotent stem cells) from mouse neonatal cardiomyocytes (CMs) by combining TGF-β signal inhibition and connexin43 (Cx43) silencing, and show that siPSCs show pluripotency in vitro and in vivo. Our novel non-insertional mutagenesis technique may provide a means for iPSC generation.
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyachi
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hino
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takamatsu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D065150:Cellular Reprogramming / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D005822:Genetic Vectors / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta