title: Enhanced OCT4 transcriptional activity substitutes for exogenous SOX2 in cellular reprogramming.
abstract: Adenoviral early region 1A (E1A) is a viral gene that can promote cellular proliferation and de-differentiation in mammalian cells, features required for the reprogramming of somatic cells to a pluripotent state. E1A has been shown to interact with OCT4, and as a consequence, to increase OCT4 transcriptional activity. Indeed, E1A and OCT4 are sufficient to revert neuroepithelial hybrids to pluripotency, as demonstrated in previous cell fusion experiments. However, the role that E1A might play in the generation of induced pluripotent stem cells (iPSCs) has not been investigated yet. In this report, we show that E1A can generate iPSCs in combination with OCT4 and KLF4, thus replacing exogenous SOX2. The generated iPSCs are bona fide pluripotent cells as shown by in vitro and in vivo tests. Overall, our study suggests that E1A might replace SOX2 through enhancing OCT4 transcriptional activity at the early stages of reprogramming.
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
authors.forename: Adele G
authors.initials: AG
authors.lastname: Marthaler
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Tiemann
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
authors.forename: Davood
authors.initials: D
authors.lastname: Sabour
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Velychko
authors.affiliation: Department of Neurology, St Josef Hospital, Ruhr University Bochum, Gudrunstraße 56, 44791 Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.|Medical Faculty, University of Münster, Domagkstraße 3, 48149 Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.|Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors