title: Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells.
abstract: The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required onlyfor the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.
authors.affiliation: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH , Baltimore, MD 21224,  USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Amano
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Nakatake
authors.forename: Misa
authors.initials: M
authors.lastname: Amano
authors.forename: Yulan
authors.initials: Y
authors.lastname: Piao
authors.forename: Hien G
authors.initials: HG
authors.lastname: Hoang
authors.forename: Minoru S H
authors.initials: MS
authors.lastname: Ko
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; C534888:Zscan4d protein, mouse