title: Successful reprogramming of epiblast stem cells by blocking nuclear localization of β-catenin.
abstract: Epiblast stem cells (EpiSCs) in mice and rats are primed pluripotent stem cells (PSCs). They barely contribute to chimeric embryos when injected into blastocysts. Reprogramming of EpiSCs to embryonic stem cell (ESC)-like cells (rESCs) may occur in response to LIF-STAT3 signaling; however, low reprogramming efficiency hampers potential use of rESCs in generating chimeras. Here, we describe dramatic improvement of conversion efficiency from primed to naive-like PSCs through upregulation of E-cadherin in the presence of the cytokine LIF. Analysis revealed that blocking nuclear localization of β-CATENIN with small-molecule inhibitors significantly enhances reprogramming efficiency of mouse EpiSCs. Although activation of Wnt/β-catenin signals has been thought desirable for maintenance of naive PSCs, this study provides the evidence that inhibition of nuclear translocation of β-CATENIN enhances conversion of mouse EpiSCs to naive-like PSCs (rESCs). This affords better understanding of gene regulatory circuits underlying pluripotency and reprogramming of PSCs.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Murayama
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Masaki
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Hayama
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5461, USA. Electronic address: nakauchi@ims.u-tokyo.ac.jp.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D023061:Gene Order; D005822:Genetic Vectors; D005855:Germ Layers / Q000166:cytology*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D053605:Leukemia Inhibitory Factor; D051820:TCF Transcription Factors; D051176:beta Catenin