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Genome-wide study of Wnt/b-catenin-mediated differentiation and maintenance of stemness

Research Project

Project/Area Number 25670851
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
Research InstitutionThe University of Tokyo

Principal Investigator

OHBA Shinsuke  東京大学, 工学(系)研究科(研究院), 准教授 (20466733)

Co-Investigator(Kenkyū-buntansha) TEI Yuichi  東京大学, 大学院工学系研究科, 教授 (30345053)
KOMIYAMA Yusuke  獨協医科大学, 医学部, 助教 (90586471)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胚性幹細胞 / Wnt / 多能性 / 分化 / βカテニン / β-カテニン / ゲノム標的
Outline of Final Research Achievements

This study aims to identify mechanisms underlying the effect of Wnt/beta-catenin pathway on the maintenance of stemness and differentiation in mouse embryonic stem cells (mESCs). We performed chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) for beta-catenin and expression profiling for Wnt/beta-catenin pathway-responsive genes in mESCs that carried epitope-tagged beta-catenin. Obtained data suggest that Wnt/beta-catenin pathway utilizes Tcf3 and pluripotency-related transcription factors for the regulation of pluripotency. In contrast, cooperative actions of Tcf3 and Ets, which acts downstream of MEK pathway, are likely to underlie the regulation of differentiation by Wnt/beta-catenin pathway. These findings may lead to the development of methods for stable supply of high-quality stem cells and efficient differentiation of stem cells.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (6 results) (of which Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Signaling pathways regulating the specification and differentiation of the osteoblast lineage2015

    • Author(s)
      Hojo H, Ohba S, Chung UI
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 57-62

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Runx1 and Runx3 are downstream effectors of Nanog in the promoted osteogenic differentiation of mesenchymal cells the mouse mesenchymal cell line C3H10T1/22014

    • Author(s)
      Saito T, Ohba S, Yano F, Seto I, Yonehara Y, Takato T, and Ogasawara T
    • Journal Title

      Cell Reprogram

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PTHrP action on skeletal development: a key for the controlled growth of endochondral bones2014

    • Author(s)
      Ohba S, Chung UI
    • Journal Title

      Clinc Rev Bone Miner Metab

      Volume: 12 Pages: 130-141

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PTHrP action on skeletal development: a key for the controlled growth of endochondral bones.2014

    • Author(s)
      Ohba S, Chung UI
    • Journal Title

      Clinc Rev Bone Miner Metab

      Volume: -

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene regulatory networks mediating canonical Wnt signal directed control of pluripotency and differentiation in embyo stem cells.2013

    • Author(s)
      Xiaoxiao Zhang
    • Journal Title

      Stem Cells

      Volume: - Issue: 12 Pages: 2667-2679

    • DOI

      10.1002/stem.1371

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation2013

    • Author(s)
      Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
    • Journal Title

      PLoS One

      Volume: 16;8(9) Issue: 9 Pages: e74137-e74137

    • DOI

      10.1371/journal.pone.0074137

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tenomodulin expression in the periodontal ligament enhances cellular adhesion2013

    • Author(s)
      Y. Komiyama, S. Ohba, N. Shimohata, K. Nakajima, H. Hojo, F. Yano, T. Takato, D. Docheva, C. Shukunami, Y. Hiraki, and UI. Chung.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e60203-e60203

    • DOI

      10.1371/journal.pone.0060203

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hedgehog-Gli activators direct osteo-chondrogenic function of bone morp hogenetic protein toward osteogenesis in the perichondrium.2013

    • Author(s)
      Hojo H, et al.
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 14 Pages: 9924-9932

    • DOI

      10.1074/jbc.m112.409342

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone healing by sterilizable calcium phosphate tetrapods eluting osteoge nic molecules.2013

    • Author(s)
      Maeda Y, Hojo H, et al.
    • Journal Title

      Biomaterials

      Volume: 34 Issue: 22 Pages: 5530-5537

    • DOI

      10.1016/j.biomaterials.2013.03.089

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions.2013

    • Author(s)
      Kanke K, Saito S, Hojo H, Lichtler AC, Chung UI, Ohba S
    • Organizer
      Cell symposia 2013- Stem cells to model and treat human disease
    • Place of Presentation
      Los Angeles, CA, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Identifying Sox9 regulatory programs in mammalian skeletogenesis.2013

    • Author(s)
      He X, McMahon AP, Ohba S
    • Organizer
      35th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Baltimore, MD, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts with four small molecules under a serum-free condition.2013

    • Author(s)
      Kanke K, Saito T, Hojo H, Lichtler AC, Chung UI, Ohba S
    • Organizer
      35th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Baltimore, MD, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Sox9による軟骨形成制御プログラムの同定.2013

    • Author(s)
      大庭伸介, Xinjun He, 鄭雄一, Andrew P. McMahon
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場、兵庫
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨格発生メカニズムの理解と骨・軟骨再生医療.2013

    • Author(s)
      大庭伸介
    • Organizer
      第55回歯科基礎医学会学術大会・総会
    • Place of Presentation
      岡山コンベンションセンター、岡山
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨芽細胞と軟骨細胞における転写ネットワークとエピジェネティクス2013

    • Author(s)
      大庭伸介
    • Organizer
      日本補綴歯科学会第122回学術大会
    • Place of Presentation
      福岡国際会議場、福岡
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 東京大学大学院工学系研究科バイオエンジニアリング専攻 教員紹介

    • URL

      http://www.bioeng.t.u-tokyo.ac.jp/faculty/36_ohba.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 1. 脊柱靭帯骨化症の病態進行抑制剤2014

    • Inventor(s)
      大庭伸介、鄭雄一、山本健一、前田祐二郎
    • Industrial Property Rights Holder
      大庭伸介、鄭雄一、山本健一、前田祐二郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-033916
    • Filing Date
      2014-02-25
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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