• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Dynamics of epigenome and transcription during the Hedgehog signaling-mediated specification of skeletal cells

Research Project

Project/Area Number 26713054
Research Category

Grant-in-Aid for Young Scientists (A)

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

Principal Investigator

Ohba Shinsuke  東京大学, 大学院医学系研究科(医学部), 准教授 (20466733)

Research Collaborator HOJO Hironori  
MCMAHON Andrew  
HE Xinjun  
TEI Yuichi  
KANKE Kosuke  
KITAURA Yoshiaki  
KASHIWAGI Miki  
ZUJUR Denise  
YAMAKAWA Akira  
PERMATASARI Galuh Wening  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2015: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsヘッジホッグ / 骨形成 / シグナル伝達 / 発生分化 / 生体分子
Outline of Final Research Achievements

The ultimate goal of this project is to understand the mechanism underlying the Hedgehog (Hh)-Gli-mediated specification of progenitors into bone-forming osteoblasts, in terms of dynamics of epigenome, transcription, and gene regulatory networks. Cell populations being at the specification phase were identified in the osteoblast differentiation system of mouse embryonic stem cells, and molecular characteristics of the populations were determined. Findings on molecular mechanisms underlying the Hh-Gli-mediated osteoblast specification were obtained by chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptional profiling in the identified population. These findings will help us establish the genome-wide molecular basis of efficacy and safety of Hh signaling in bone regenerative therapies.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (44 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 8 results,  Acknowledgement Compliant: 7 results) Presentation (26 results) (of which Int'l Joint Research: 9 results,  Invited: 10 results) Remarks (2 results)

  • [Int'l Joint Research] the University of Southern California/University of Connecticut Health Center(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] 南カリフォルニア大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] 南カリフォルニア大学(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions2017

    • Author(s)
      Zujur D, Kanke K, Lichtler AC, Hojo H, Chung UI, Ohba S
    • Journal Title

      Science Advanvces

      Volume: 3 Issue: 5

    • DOI

      10.1126/sciadv.1602875

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the gene-regulatory landscape in skeletal development and potential links to skeletal regeneration.2017

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

      Regenerative Therapy

      Volume: 6 Pages: 100-107

    • DOI

      10.1016/j.reth.2017.04.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-layered mutatin in hedgehog-related genes in Gorlin syndrome may affect the phenotype.2017

    • Author(s)
      Onodera S, Saito A, Hasegawa D, Watanabe K, Morita N, Nomura T, Shibahara T, Ohba S, Yamaguchi A, Azuma T
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 9 Pages: e0184702-e0184702

    • DOI

      10.1371/journal.pone.0184702

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AP-1 family members act with Sox9 to promote chondrocyte hypertrophy.2016

    • Author(s)
      He X, Ohba S (co-first), Hojo H, McMahon AP
    • Journal Title

      Development

      Volume: 143 Issue: 16 Pages: 3012-3023

    • DOI

      10.1242/dev.134502

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Local administration of a hedgehog agonist accelerates fracture7healing in a mouse model.2016

    • Author(s)
      Kashiwagi M, Hojo H, Kitaura Y, Maeda Y, Aini H, Takato T, Chung U, Ohba S.
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 479 Issue: 4 Pages: 772-778

    • DOI

      10.1016/j.bbrc.2016.09.134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hedgehog signaling in endochondral ossification.2016

    • Author(s)
      Ohba S
    • Journal Title

      10.3390/jdb4020020

      Volume: 4 Pages: 20-20

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An emerging regulatory landscape for skeletal development.2016

    • Author(s)
      Hojo H, McMahon AP, *Ohba S
    • Journal Title

      Trends Genet

      Volume: 32 Issue: 12 Pages: 774-787

    • DOI

      10.1016/j.tig.2016.10.001

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sp7/Osterix is restricted to bone-forming vertebrates where it acts as a Dlx co-factor in osteoblast specification.2016

    • Author(s)
      Hojo H, Ohba S, He X, Lai LP, McMahon AP
    • Journal Title

      Dev Cell

      Volume: 37 Issue: 3 Pages: 238-253

    • DOI

      10.1016/j.devcel.2016.04.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte.2015

    • Author(s)
      Ohba S, He X, Hojo H, McMahon AP
    • Journal Title

      Cell Reports

      Volume: 12(2) Issue: 2 Pages: 229-243

    • DOI

      10.1016/j.celrep.2015.06.013

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The H2 blocker famotidine suppresses progression of ossification of the posterior longitudinal ligament in a mouse model.2015

    • Author(s)
      Maeda Y, Yamamoto K, Yamakawa A, Aini H, Takato T, Chung UI, Ohba S
    • Journal Title

      RMD Open

      Volume: 1 Issue: 1 Pages: e000068-e000068

    • DOI

      10.1136/rmdopen-2015-000068

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Runx1 and Runx3 Are Downstream Effectors of Nanog in Promoting Osteogenic Differentiation of the Mouse Mesenchymal Cell Line C3H10T1/22015

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

      Cell Reprogram

      Volume: 17 Issue: 3 Pages: 227-234

    • DOI

      10.1089/cell.2014.0059

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2.2015

    • Author(s)
      Sugita S, Taketomi S, Saito T, et al.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112 Issue: 10 Pages: 3080-5

    • DOI

      10.1073/pnas.1419699112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Signaling pathways regulating the specification and differentiation of the osteoblast lineage2015

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

      Regenerative Therapy

      Volume: 1 Pages: 57-62

    • DOI

      10.1016/j.reth.2014.10.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 骨格形成における遺伝子発現機構をゲノムスケールで理解する2018

    • Author(s)
      大庭伸介
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Hedgehog agonist promotes callus formation in a mouse fracture model.2017

    • Author(s)
      Kashiwagi M, Hojo H, Kitaura Y, Maeda Y, Aini H, Takato T, Chung UI, Ohba S
    • Organizer
      IADR/AADR/CADR General Session & Exhibition
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2017-03-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancer network for Ihh transcription in chondrocytes.2017

    • Author(s)
      Yamakawa A, Hojo H, Chung UI, Ohba S
    • Organizer
      Orthopaedic Research Society (ORS) 2017 Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2017-03-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct transcriptional program underlie Sox9 regulation of the mammalian chondrocyte.2017

    • Author(s)
      大庭伸介
    • Organizer
      第30回軟骨代謝学会
    • Place of Presentation
      京都勧業館みやこめっせ(京都府京都市)
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 軟骨細胞におけるエンハンサーネットワークを介したIndian hedgehogの発現制御機構.2017

    • Author(s)
      山川晃, 北條宏徳, 鄭雄一, 大庭伸介
    • Organizer
      第30回軟骨代謝学会
    • Place of Presentation
      京都勧業館みやこめっせ(京都府京都市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨格形成における遺伝子発現機構をゲノムスケールで理解する2017

    • Author(s)
      大庭伸介
    • Organizer
      第59回歯科基礎医学会学術大会・総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Modeling of bone remodeling by three-dimensional co-culture of mouse embryonic stem cell-derived osteoblasts and osteoclast precursors.2017

    • Author(s)
      Zujur DC, Hikita A, Kanke K, Hojo H, Chung UI, Ohba S
    • Organizer
      Joint meeting of the Australian & New Zealand Bone and Mineral Society & the International Federation of Musculoskeletal Research Societies
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟骨細胞特異的なIhhのエンハンサーの同定とSox9によるその活性化機構2017

    • Author(s)
      山川晃, 北條宏徳, 鄭雄一, 大庭伸介
    • Organizer
      第35回日本骨代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Gorlin症候群患者由来iPS細胞の骨芽細胞分化能の異常とその分子メカニズム2017

    • Author(s)
      小野寺晶子, 東俊文, 斎藤暁子, 長谷川大悟, 片倉朗, 野村武史, 小崎健次郎, 鄭雄一, 大庭伸介
    • Organizer
      第35回日本骨代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 軟骨細胞におけるエンハンサーネットワークを介したIndian hedgehogの発現制御機構2017

    • Author(s)
      山川晃, 北條宏徳, 鄭雄一, 大庭伸介
    • Organizer
      第90回日本整形外科学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 軟骨細胞におけるIndian hedgehogの発現制御機構.2016

    • Author(s)
      山川晃, 北條宏徳, 鄭雄一, 大庭伸介
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulatory mechanisms underlying Ihh transcription in chondrocytes.2016

    • Author(s)
      Yamakawa A, Chung UI, Ohba S
    • Organizer
      38th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨形成の分子メカニズムとその骨再生への応用.2016

    • Author(s)
      大庭伸介
    • Organizer
      日本セラミックス協会第29回秋季シンポジウム
    • Place of Presentation
      広島大学東広島キャンパス(広島県東広島市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Differentiation of mouse pluripotent stem cells in three-dimensional cultures under defined conditions.2016

    • Author(s)
      Zujur DC, Kanke K, Chung UI, Ohba S
    • Organizer
      International Society for Stem Cell Research (ISSCR) 14th Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞の段階的骨芽細胞分化誘導とその応用.2015

    • Author(s)
      大庭伸介
    • Organizer
      第26回日本小児整形外科学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts using small molecules under defined conditions.2015

    • Author(s)
      Ohba S
    • Organizer
      2015 International Congress of Osteoporosis (ICO)
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-11-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 医工の融合によるメディカルイノベータ-創出.2015

    • Author(s)
      大庭伸介
    • Organizer
      第67回日本気管食道科学会総会・学術講演会
    • Place of Presentation
      ザ・セレクトン福島(福島県福島市)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] An Sp7/Dlx transcriptional complex specifies mammalian osteoblasts.2015

    • Author(s)
      Hojo H, Ohba S, He X, Lai LP, McMahon AP
    • Organizer
      37th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct modes of Sox9 action in the transcriptional regulation of developing mammalian chondrocytes.2015

    • Author(s)
      Ohba S, He X, Hojo H, McMahon AP
    • Organizer
      37th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] AP-1 factor interacts with Sox9 during mammalian chondrocyte hypertrophy.2015

    • Author(s)
      He X, Ohba S, Hojo H, McMahon AP
    • Organizer
      37th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞の段階的骨芽細胞分化誘導法の開発とその応用.2015

    • Author(s)
      大庭伸介
    • Organizer
      第33回日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 低分子化合物4種と無血清培地を用いた多能性幹細胞からの骨芽細胞分化誘導法の開発.2015

    • Author(s)
      菅家康介, 齋藤琢, 高戸毅, 鄭雄一, 大庭伸介
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜、神奈川県
    • Year and Date
      2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Gli1 haploinsufficiency disrupts postnatal bone homeostasis under physiological and pathological conditions.2014

    • Author(s)
      Kitaura Y, Hojo H, Komiyama Y, Takato T, Chung UI, Ohba S
    • Organizer
      36th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Houston, USA
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions2014

    • Author(s)
      Kanke K, Masaki H, Saito S, Komiyama Y, Hojo H, Lichtler AC, Nakauchi H, Takato T, Chung UI, Ohba S
    • Organizer
      International Society for Stem Cell Research 12th Annual Meeting
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低分子化合物を用いた多能性幹細胞の骨芽細胞分化誘導法の開発とその応用の可能性2014

    • Author(s)
      大庭伸介
    • Organizer
      第68回日本口腔科学会学術集会シンポジウム iPS細胞が拓く未来の医療 骨/軟骨研究の進歩
    • Place of Presentation
      京王プラザホテル、東京都
    • Year and Date
      2014-05-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ヘッジホッグシグナルによる骨形成の制御2014

    • Author(s)
      大庭伸介
    • Organizer
      第87回日本内分泌学会学術総会シンポジウム9 骨軟骨代謝ネットワークと細胞連関
    • Place of Presentation
      福岡国際会議場、福岡県
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 東京大学鄭雄一研究室大庭・鄭グループ ホームページ

    • URL

      http://www.tetrapod.t.u-tokyo.ac.jp/ohba-tei/achivement.html

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [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

URL: 

Published: 2014-04-04   Modified: 2022-02-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi