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Mechanistic analysis of the circadian clock development in mammals

Research Project

Project/Area Number 23390051
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

YAGITA Kazuhiro  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90324920)

Co-Investigator(Kenkyū-buntansha) INOKAWA Hitoshi  京都府立医科大学, 医学研究科, 講師 (40285250)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords体内時計 / 細胞分化 / ES細胞 / 発生 / 概日リズム / 幹細胞 / 分化誘導 / RNA-seq / イメージング
Outline of Final Research Achievements

In mammals, the emergence of circadian clock oscillation gradually occurs during the developmental process. However, developmental mechanisms of circadian clock have not been well understood.
We have shown that the circadian clock oscillation is not detected in the mouse embryonic stem (ES) cells. We also showed that the apparent circadian clock oscillation is induced during the differentiation culture of mouse ES cells without maternal entraining factors. These results demonstrate that the intrinsic program controls the circadian oscillator formation during the differentiation process of ES cells in cultural condition.
To understand the circadian clock development in mammals, we performed ES cell-based screening to find out factors contributing to the clock formation mechanisms, and found Dnmt1 as an essential factor for circadian clock development. Epigenetic programming and following organization of transcriptional network may be essential for circadian clock development in mammals.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (33 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (25 results) (of which Invited: 20 results)

  • [Journal Article] Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur.2015

    • Author(s)
      Okubo N, Fujiwara H, Minami Y, Kunimoto T, Hosokawa T, Umemura Y, Inokawa H, Asada M, Oda R, Kubo T, Yagita K.
    • Journal Title

      Acta Orthopedica

      Volume: 13 Issue: 5 Pages: 1-5

    • DOI

      10.3109/17453674.2015.1029393

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transcriptional Program of Kpna2 /Importin-α2 Regulates Cellular Differentiation-Coupled Circadian Clock Development in Mammalian Cells.2014

    • Author(s)
      Umemura Y, Koike N, Matsumoto T, Yoo S-H, Zhen C, Yasuhara N, Takahashi JS, Yagita K.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 111 Issue: 47 Pages: 5039-48

    • DOI

      10.1073/pnas.1419272111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cell and Tissue-autonomous development of the circadian clock in mouse embryos.2014

    • Author(s)
      Inada Y, Uchida H, Umemura Y, Nakamura W, Sakai T, Koike N, Yagita K.
    • Journal Title

      FEBS Lett

      Volume: 588 Issue: 3 Pages: 459-465

    • DOI

      10.1016/j.febslet.2013.12.007

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock.2013

    • Author(s)
      Engelen E, Janssens RC, Yagita K, Smits VA, van der Horst GT, Tamanini F
    • Journal Title

      PLoS One

      Volume: 8 Issue: 2 Pages: e56623-e56623

    • DOI

      10.1371/journal.pone.0056623

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro ES cell-based clock recapitulation assay model identifies CK2a as an endogenous clock regulator2013

    • Author(s)
      Umemura Y, Yoshida J, Wada M, Tsuchiya Y, Minami Y, Watanabe H, Kondoh G, Takeda J, Inokawa H, Horie K, Yagita K.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 6 Pages: e67241-e67241

    • DOI

      10.1371/journal.pone.0067241

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regional circadian period difference in the suprachiasmatic nucleus of the mammalian circadian center.2013

    • Author(s)
      Koinuma S, Asakawa T, Nagano M, Furukawa K, Sujino M, Masumoto KH, Nakajima Y, Hashimoto S, Yagita K, Shigeyoshi Y.
    • Journal Title

      Eur J Neurosci.

      Volume: 38 Issue: 6 Pages: 2832-41

    • DOI

      10.1111/ejn.12308

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prolonged Bioluminescence Monitoring in Mouse ex vivo Bone Culture Revealed Persistent Circadian Rhythms in Articular Cartilages and Growth Plates.2013

    • Author(s)
      Okubo N, Minami Y, Fujiwara H, Umemura Y, Tsuchiya Y, Shirai Y, Oda R, Inokawa H, Kubo T, Yagita K*.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e78306-e78306

    • DOI

      10.1371/journal.pone.0078306

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The prtorous CPD photolyase rescues a cryptochrome-deficient mammalian circadian clock2011

    • Author(s)
      Chaves I, Nijman RM, Biernat MA, Bajek MI, de Silva AC, Saito S, Yagita K, Eker AP, van der Horst GT
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Epigenetic and Molecular mechanisms suppressing circadian clock in pluripotent stem cells.2015

    • Author(s)
      Yagita K.
    • Organizer
      4th International Symposium on Molecular Clock 2015
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 概日時計の発生から細胞を考える.2014

    • Author(s)
      八木田和弘
    • Organizer
      細胞センサーの分子機構・相互関連・ネットワーク研究会
    • Place of Presentation
      岡崎
    • Year and Date
      2014-12-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 革新的技術による哺乳類概日時計の統合的理解.2014

    • Author(s)
      八木田和弘
    • Organizer
      第21回日本時間生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 生殖と発生の時間生物学.2014

    • Author(s)
      八木田和弘
    • Organizer
      第67回日本自律神経学会総会
    • Place of Presentation
      さいたま
    • Year and Date
      2014-10-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Cellular Differentiation and Circadian Clock in Mammalian Cells.2014

    • Author(s)
      Yagita K.
    • Organizer
      Fujihara Seminar 2014
    • Place of Presentation
      Izu
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 生殖の時間生物学.2014

    • Author(s)
      八木田和弘
    • Organizer
      第17回日本IVF学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Effect of MeCP2 on Molecular Clock Development in the SCN.2014

    • Author(s)
      八木田和弘
    • Organizer
      第37回日本神経科学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 生殖と概日リズム.2014

    • Author(s)
      八木田和弘
    • Organizer
      第43回日本女性心身医学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-08-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Molecular Mechanisms of Circadian clock development in mammalian cells.2014

    • Author(s)
      Yagita K.
    • Organizer
      The 30th Anniversary of Sapporo Symposium on Biological Rhythms
    • Place of Presentation
      Sapporo
    • Year and Date
      2014-07-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 体内時計の分子機構.2014

    • Author(s)
      八木田和弘
    • Organizer
      第14回日本抗加齢医学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞分化に伴う体内時計発生メカニズム.2014

    • Author(s)
      八木田和弘
    • Organizer
      京都大学再生医科学研究所公開シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2014-05-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Circadian clock and cellular differentiation2012

    • Author(s)
      八木田和弘
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本
    • Year and Date
      2012-03-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] ES cell-based evaluation system of circadian phenotypes in mammals.2012

    • Author(s)
      Kazuhiro Yagita
    • Organizer
      13th Society for Research on Biological Rhythms
    • Place of Presentation
      Destin, Florida
    • Related Report
      2012 Annual Research Report
  • [Presentation] Circadian Clock and Cellular Differentiation : Development, Regeneration and Cancer2011

    • Author(s)
      八木田和弘
    • Organizer
      第34回日本分子生物学会年会ワークショップ
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胞分化と概日時計の発生2011

    • Author(s)
      八木田和弘
    • Organizer
      第64回日本自律神経学会
    • Place of Presentation
      秋田
    • Year and Date
      2011-10-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Chronogenesis and Cellular Differentiation2011

    • Author(s)
      Kazuhiro Yagita
    • Organizer
      Gordon Research Conferences : Chronobiology
    • Place of Presentation
      イタリア ルッカ
    • Year and Date
      2011-06-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] Circadian Clock: A cell-autonomous time-keeping system in our body.

    • Author(s)
      Kazuhiro Yagita
    • Organizer
      6th Asia Oceania Conference of Photobiology,
    • Place of Presentation
      Sydney
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Misregulation of transcriptional program controlling the cellular differentiation resulted in disruption of the circadian clock development.

    • Author(s)
      八木田和弘
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ES細胞を用いた概日時計のin vitro再現と分化制御機構との関連

    • Author(s)
      八木田和弘
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] MYC induced disruption of circadian clock development

    • Author(s)
      八木田和弘
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 体内時計はいつ動き出すか

    • Author(s)
      八木田和弘
    • Organizer
      第14回日本抗加齢医学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ES cell-based approach elucidating the integrated physiology of mammalian circadian systems.

    • Author(s)
      Kazuhiro Yagita
    • Organizer
      4th International Symposium on Photic Bioimaging 2012
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Cell-autonomous development of mammalian circadian clock during the differentiation culture of ES cells.

    • Author(s)
      Kazuhiro Yagita
    • Organizer
      International Conference for Histochemistry and Cytochemistry 2012
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 体内時計の発生・発達

    • Author(s)
      八木田和弘
    • Organizer
      第1回日本発達神経科学会
    • Place of Presentation
      明石
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 時間軸生物学:細胞分化と概日時計の接点

    • Author(s)
      八木田和弘
    • Organizer
      第12回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
    • Invited

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Published: 2011-04-06   Modified: 2019-07-29  

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