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

• Project/Area Number: 25670851
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] Signaling pathways regulating the specification and differentiation of the osteoblast lineage (2015)
  • Author(s): Hojo H, Ohba S, Chung UI
  • Journal Title: Regenerative Therapy Volume: 1 Pages: 57-62
  • 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 C3H10T1/2 (2014)
  • Author(s): Saito T, Ohba S, Yano F, Seto I, Yonehara Y, Takato T, and Ogasawara T
  • Journal Title: Cell Reprogram Volume: -
  • 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: 12 Pages: 130-141
  • 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: -
  • 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
  • Peer Reviewed
• [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Tenomodulin expression in the periodontal ligament enhances cellular adhesion (2013)
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
  • 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
  • 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
• [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