title: Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A Dramatically Improves Efficiency and Kinetics of Reprogramming to Induced Pluripotent Stem Cells.
abstract: Identification of a gene set capable of driving rapid and proper reprogramming to induced pluripotent stem cells (iPSCs) is an important issue. Here we show that the efficiency and kinetics of iPSC reprogramming are dramatically improved by the combined expression of Jarid2 and genes encoding its associated proteins. We demonstrate that forced expression of JARID2 promotes iPSC reprogramming by suppressing the expression of Arf, a known reprogramming barrier, and that the N-terminal half of JARID2 is sufficient for such promotion. Moreover, JARID2 accelerated silencing of the retroviral Klf4 transgene and demethylation of the Nanog promoter, underpinning the potentiating activity of JARID2 in iPSC reprogramming. We further show that JARID2 physically interacts with ESRRB, SALL4A, and PRDM14, and that these JARID2-associated proteins synergistically and robustly facilitate iPSC reprogramming in a JARID2-dependent manner. Our findings provide an insight into the important roles of JARID2 during reprogramming and suggest that the JARID2-associated protein network contributes to overcoming reprogramming barriers.
authors.affiliation: Division of Functional Genomics and Systems Medicine, Saitama Medical University, Saitama, Japan.|CREST, Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Iseki
authors.affiliation: Division of Functional Genomics and Systems Medicine, Saitama Medical University, Saitama, Japan.|Division of Translational Research, Saitama Medical University, Saitama, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakachi
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.|CREST, Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hishida
authors.affiliation: Division of Functional Genomics and Systems Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Yzumi
authors.initials: Y
authors.lastname: Yamashita-Sugahara
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Hirasaki
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.affiliation: Laboratory Animal Resource Center, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanimoto
authors.affiliation: Laboratory Animal Resource Center, University of Tsukuba, Ibaraki, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Iijima
authors.affiliation: Laboratory Animal Resource Center, University of Tsukuba, Ibaraki, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.affiliation: Laboratory Animal Resource Center, University of Tsukuba, Ibaraki, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yagami
authors.affiliation: CREST, Japan Science and Technology Agency (JST), Saitama, Japan.|Laboratory Animal Resource Center, University of Tsukuba, Ibaraki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.|CREST, Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuda
authors.affiliation: Division of Functional Genomics and Systems Medicine, Saitama Medical University, Saitama, Japan.|Division of Translational Research, Saitama Medical University, Saitama, Japan.|CREST, Japan Science and Technology Agency (JST), Saitama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C098925:Esrrb protein, mouse; C093650:Jarid2 protein, mouse; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C531066:Prdm14 protein, mouse; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; C509167:Sall4 protein, mouse; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2
keywords: ESRRB; Induced pluripotent stem cell; JARID2; PRDM14; Reprogramming; SALL4