Identification of osteogenic transcriptional networks by chromatin immunoprecipitation sequencing and genetic approaches

• Project/Area Number: 23689079
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• 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)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000); Fiscal Year 2013: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
• Keywords: 骨芽細胞 / 転写 / 骨形成 / 転写ネットワーク

Outline of Final Research Achievements

This study aims to determine molecular mechanisms through which transcriptional regulators that are required for skeletal formation regulate differentiation of skeletal progenitors. Chromatin immunoprecipitation sequencing (ChIP-seq) and expression profiling in mouse primary osteoblasts and chondrocytes identified binding regions and target genes of the regulators in a genome-wide manner. Bioinformatic analyses of the data set provided genome-wide evidences for modes of action of each factor and its biological significance. These findings may help us understand mechanisms underlying the regulation of skeletal formation and lead to basic knowledge to achieve skeletal regenerative medicine.

Research Products

• [Journal Article] Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions. (2014)
  • Author(s): Kanke K, Masaki H, Saito T, Komiyama Y, Hojo H, Nakauchi H, Lichtler AC, Takato T, Chung UI, Ohba S
  • Journal Title: Stem Cell Reports. Volume: 6 Issue: 6 Pages: 751-760
  • DOI: 10.1016/j.stemcr.2014.04.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gli1 haploinsufficiency leads to decreased bone mass with an uncoupling of bone metabolism in adult mice. (2014)
  • Author(s): Kitaura Y, Hojo H, Komiyama Y, Takato T, Chung UI, Ohba S
  • Journal Title: PLoS ONE Volume: 9(10) Issue: 10 Pages: e109597-e109597
  • DOI: 10.1371/journal.pone.0109597
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Bioactive factors for tissue regeneration: State of Art. (2012)
  • Author(s): Shinsuke Ohba
  • Journal Title: Muscles, Ligaments and Tendons Journal Volume: 2 Pages: 193-203
  • Peer Reviewed
• [Journal Article] Current progress on tissue engineering of bone and cartilage. (2012)
  • Author(s): Shinsuke Ohba
  • Journal Title: Endocrinology and Metabolism Volume: 27 Issue: 1 Pages: 1-11
  • DOI: 10.3803/enm.2012.27.1.1
  • Peer Reviewed
• [Journal Article] Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification (2012)
  • Author(s): Hojo H, 他
  • Journal Title: J Biol Chem Volume: 287 Issue: 21 Pages: 17860-17869
  • DOI: 10.1074/jbc.m112.347716
  • Peer Reviewed
• [Journal Article] Famotidine suppresses osteogenic differentiation of tendon cells in vitro and pathological calcification of tendon in vivo (2012)
  • Author(s): Yamamoto K, Hojo H, 他
  • Journal Title: J Orthop Res Volume: 30 Issue: 12 Pages: 1958-1962
  • DOI: 10.1002/jor.22146
  • Peer Reviewed
• [Journal Article] Current Progress on Tissue Engineering of Bone and Cartilage (2012)
  • Author(s): Shinsuke Ohba
  • Journal Title: Endocrinology and Metabolism Volume: (In press)(印刷中)(掲載確定)
  • Peer Reviewed
• [Presentation] Identification of distinct modes of Sox9 action in chondrocytes. (2014)
  • Author(s): Shinsuke Ohba
  • Organizer: 4th International SOX Research Conference
  • Place of Presentation: Cleveland, OH, USA
  • Year and Date: 2014-09-11
  • Invited
• [Presentation] 軟骨細胞ゲノムにおけるSox9作動様式の解析 (2014)
  • Author(s): 大庭伸介
  • Organizer: 第15回運動器科学研究会
  • Place of Presentation: ベルサール三田、東京
  • Year and Date: 2014-09-05
• [Presentation] Gli1 Participates in the Indian Hedgehog-mediated Osteogenesis during Endochondral Ossification. (2012)
  • Author(s): Hironori Hojo
  • Organizer: 34th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis, MN, USA
• [Presentation] Osteo-chondrogenic Function of BMP is Directed Toward Osteogenesis by Hh-Gli1 in the Perichondrium. (2012)
  • Author(s): Hironori Hojo
  • Organizer: 34th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis, MN, USA
• [Presentation] Development of a Novel Tetrapod-shaped Drug-eluting Artificial Bone. (2012)
  • Author(s): Yujiro Maeda
  • Organizer: 34th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis, MN, USA
• [Presentation] Understanding the Regulatory Networks in Chondrocyte Development. (2012)
  • Author(s): Xinjun He
  • Organizer: Cold Spring Harbor Asia Conferences Bone and Cartilage: from Development to Human Diseases
  • Place of Presentation: Suzhou, China
• [Presentation] 遺伝学的手法と組み合わせたクロマチン免疫沈降-シーケンス法の骨軟骨生物学への応用 (2011)
  • Author(s): 大庭伸介
  • Organizer: 日本動物細胞工学会
  • Place of Presentation: 東京大学山上会館(東京都)
  • Year and Date: 2011-07-22
• [Book] 多能性幹細胞を使った骨再生, 再生医療叢書 6 骨格系 (2012)
  • Author(s): 大庭伸介
  • Total Pages: 178
  • Publisher: 朝倉書店
• [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
• [Remarks] 東京大学大学院工学系研究科
  • URL: http://www.t.u-tokyo.ac.jp/tpage/
• [Remarks] 東京大学鄭雄一研究室
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/med/index.html
• [Remarks]
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/med/index.html