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Functional development of circadian regulation system

Research Project

Project/Area Number 18H02600
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48020:Physiology-related
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)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords概日リズム / 体内時計 / 発生学 / 細胞分化 / 母子同調 / 機能発生学 / 体節形成 / 分節時計 / 発生
Outline of Final Research Achievements

Previously, we found that ES cells and early embryo cells do not display discernible circadian oscillation, whereas circadian clock oscillation appears after in vitro differentiation culture. Moreover, we have revealed that the circadian clocks are re-disappeared when differentiated cells are reprogrammed to regain pluripotency, indicating that the emergence of circadian clock is programmed tightly linked with cellular differentiation. We showed that the development of the mammalian circadian clock requires two steps. The first is an epigenetic and transcriptional program-mediated cellular differentiation process (cell-lineage determination process), and the second is the establishment of the circadian feedback loops, in which the post-transcriptional regulation of Clock functions as a rate-modulating mechanism. These sequential mechanisms may explain, at least in part, the late emergence of mammalian circadian clock oscillation in the developmental process (Umemura et al, PNAS, 2017).

Academic Significance and Societal Importance of the Research Achievements

現在、都市機能の24時間化(24時間社会)のみならず、急速なIoT化や超少子高齢化(2025年問題)など、社会構造の大きな変化に直面している。本研究開発課題である概日リズム障害による複合的脳病態は、単に交替制勤務者の健康問題のみならず、トラックやバス等の事故、病院・警察・消防などの社会インフラ維持などとも関連する。これらの諸課題は近未来の社会が直面するリアルな問題である。本研究課題では、日常生活に起因する健康課題として非常に社会的な要請が高まっている概日リズム障害の病態解明に必須である、概日リズムの成立原理とそのメカニズムの解明を進めた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (34 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (17 results) (of which Int'l Joint Research: 5 results,  Invited: 17 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] テキサス大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Effects of constant light exposure on allergic and irritant contact dermatitis in mice reared under constant light conditions2021

    • Author(s)
      2.Mizutani H, Tamagawa-Mineoka R, Yasuike R, Minami Y, Yagita K, Katoh N.
    • Journal Title

      Experimental Dermatol

      Volume: in press Issue: 5 Pages: 739-744

    • DOI

      10.1111/exd.14308

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circadian regulation of chemotherapy-induced peripheral neuropathic pain and the underlying transcriptomic landscape2020

    • Author(s)
      Kim Hee Kee、Lee Sun-Yeul、Koike Nobuya、Kim Eunju、Wirianto Marvin、Burish Mark J.、Yagita Kazuhiro、Lee Hyun Kyoung、Chen Zheng、Chung Jin Mo、Abdi Salahadin、Yoo Seung-Hee
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13844-13844

    • DOI

      10.1038/s41598-020-70757-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circadian clock and cancer: From a viewpoint of cellular differentiation2020

    • Author(s)
      Tsuchiya Yoshiki, Umemura Yasuhiro, Yagita Kazuhiro
    • Journal Title

      International Journal of Urology

      Volume: - Issue: 6 Pages: 518-524

    • DOI

      10.1111/iju.14231

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of the Circadian Core Machinery in Mammals2020

    • Author(s)
      Umemura Yasuhiro, Yagita Kazuhiro
    • Journal Title

      Journal of Molecular Biology

      Volume: - Issue: 12 Pages: 3611-3617

    • DOI

      10.1016/j.jmb.2019.11.026

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice2020

    • Author(s)
      Inokawa Hitoshi, Umemura Yasuhiro, Shimba Akihiro, Kawakami Eiryo, Koike Nobuya, Tsuchiya Yoshiki, Ohashi Munehiro, Minami Yoichi, Cui Guangwei, Asahi Takuma, Ono Ryutaro, Sasawaki Yuh, Konishi Eiichi, Yoo Seung-Hee, Chen Zheng, Teramukai Satoshi, Ikuta Koichi, Yagita Kazuhiro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2569-2569

    • DOI

      10.1038/s41598-020-59541-y

    • NAID

      120006799241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Incremental Growth Lines in Mouse Molar Dentin Represent 8-hr Ultradian Rhythm2019

    • Author(s)
      Ono Ryutaro, Koike Nobuya, Inokawa Hitoshi, Tsuchiya Yoshiki, Umemura Yasuhiro, Yamamoto Toshiro, Kanamura Narisato, Yagita Kazuhiro
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 52 Issue: 6 Pages: 93-99

    • DOI

      10.1267/ahc.19017

    • NAID

      130007776198

    • ISSN
      0044-5991, 1347-5800
    • Year and Date
      2019-12-27
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma2019

    • Author(s)
      Inoue M, Tsuchiya Y, Koike N, Umemura Y, Inokawa H, Togashi Y, Maniwa J, Higashi M, Fumino S, Tajiri T, Yagita K
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 12 Pages: 1403-1411

    • DOI

      10.1007/s00383-019-04568-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Circadian Molecular Oscillation Development Using Induced Pluripotent Stem Cells.2019

    • Author(s)
      Umemura Y, Maki I, Tsuchiya Y, Koike N, Yagita K
    • Journal Title

      J Biol Rhythms

      Volume: 34 Issue: 5 Pages: 525-532

    • DOI

      10.1177/0748730419865436

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output2019

    • Author(s)
      Ikeda Ryosuke、Tsuchiya Yoshiki、Koike Nobuya、Umemura Yasuhiro、Inokawa Hitoshi、Ono Ryutaro、Inoue Maho、Sasawaki Yuh、Grieten Tess、Okubo Naoki、Ikoma Kazuya、Fujiwara Hiroyoshi、Kubo Toshikazu、Yagita Kazuhiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10171-10171

    • DOI

      10.1038/s41598-019-46656-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity2019

    • Author(s)
      Doi Masao、Shimatani Hiroyuki、Atobe Yuta、Murai Iori、Hayashi Hida、Takahashi Yukari、Fustin Jean-Michel、Yamaguchi Yoshiaki、Kiyonari Hiroshi、Koike Nobuya、Yagita Kazuhiro、Lee Choogon、Abe Manabu、Sakimura Kenji、Okamura Hitoshi
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 2563-2563

    • DOI

      10.1038/s41467-019-10532-2

    • NAID

      120006644061

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth.2019

    • Author(s)
      Oshima T, Niwa Y, Kuwata K, Srivastava A, Hyoda T, Tsuchiya Y, Kumagai M, Tsuyuguchi M, Tamaru T, Sugiyama A, Ono N, Zolboot N, Aikawa Y, Oishi S, Nonami A, Arai F, Hagihara S, Yamaguchi J, Tama F, Kunisaki Y, Yagita K, Ikeda M, Kinoshita T, Kay SA, Itami K, Hirota T.
    • Journal Title

      Science Advance

      Volume: 23 Issue: 1 Pages: 9060-9060

    • DOI

      10.1126/sciadv.aau9060

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 概論:リアルワールドと向き合う体内時計・概日リズム研究の未来2019

    • Author(s)
      八木田和弘
    • Journal Title

      実験医学 (実験医学「特集:時間生物学からサーカディアン・メディシンへ」の企画を担当)

      Volume: 37 Pages: 352-357

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] リバーストランスレーショナル研究としてのマウスコホート2019

    • Author(s)
      井之川仁, 梅村康浩, 八木田和弘
    • Journal Title

      実験医学

      Volume: 37 Pages: 372-378

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Identification of circadian clock modulators from existing drugs2018

    • Author(s)
      T. Katherine Tamai, Yusuke Nakane, Wataru Ota, Akane Kobayashi, Masateru Ishiguro, Naoya Kadofusa, Keisuke Ikegami, Kazuhiro Yagita, Yasufumi Shigeyoshi, Masaki Sudo, Taeko Nishiwaki-Ohkawa, Ayato Sato, & Takashi Yoshimura
    • Journal Title

      EMBO Molecular Medicine

      Volume: - Issue: 5

    • DOI

      10.15252/emmm.201708724

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Circadian Clock-mediated Transition of Physiological State in Developmental and Ageing Process in Mice2020

    • Author(s)
      Yagita K
    • Organizer
      Biannual Meeting of Society for Research on Biological Rhythm 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Circadian clock-mediated state dynamics in developmental and ageing processes in mammals2020

    • Author(s)
      八木田和弘
    • Organizer
      第43回日本分子生物学 ワークショップ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウスコホートモデルのディープフェノタイプ研究:概日リズム撹乱による状態遷移2020

    • Author(s)
      八木田和弘
    • Organizer
      第93回日本生化学会大会 シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 概日リズム撹乱がもたらす病態2020

    • Author(s)
      八木田和弘
    • Organizer
      第54回糖尿病学の進歩
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 子どもの体内時計と生活リズム2020

    • Author(s)
      八木田和弘
    • Organizer
      第40回京都保育問題研究会(京都)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Developmental Program and Environmental Reprogram of Mammalian Circadian Regulation System2019

    • Author(s)
      Yagita Kazuhiro
    • Organizer
      European Biological Rhythms Society Congress 2019 (Lyon)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 体内時計はいつ形成されるか?2019

    • Author(s)
      八木田和弘
    • Organizer
      第7回新胎児学研究会(高松)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 概日リズムと老化2019

    • Author(s)
      八木田和弘
    • Organizer
      第34回老化促進モデルマウス(SAM)学会学術集会(高松)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 長期にわたる概日リズム撹乱による免疫恒常性破綻2019

    • Author(s)
      八木田和弘
    • Organizer
      第44回日本睡眠学会学術集会(名古屋)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 哺乳類細胞の概日制御系成立プログラム2019

    • Author(s)
      八木田和弘
    • Organizer
      細胞自在操作のための分子科学技術の開発拠点形成2018年度成果報告会(京田辺)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Developmental Program and Environmental Reprogramming of the Mammalian Circadian System.2019

    • Author(s)
      Yagita K.
    • Organizer
      Advance in Sleep and Circadian Science (Clearwater Beach Florida)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Developmental Program and Environmental Reprogramming of the Mammalian Circadian System.2019

    • Author(s)
      Yagita K.
    • Organizer
      Biochemistry & Molecular Biology Seminar Series: UT medical Science Center at Houston (Houston)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulation and mis-regulation of cellular differentiation-coupled circadian clock functionality in mammals.2018

    • Author(s)
      Yagita K.
    • Organizer
      Matrix Biology Europe 2018 (Manchester)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Plasticity of Mammalian Circadian Clock: from cellular to organismal levels.2018

    • Author(s)
      Yagita K.
    • Organizer
      Sapporo Symposium on Biological Rhythm in 2018 (Sapporo)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Circadian Clock and ES cell System: Differentiation, Development and Cancer.2018

    • Author(s)
      Yagita K.
    • Organizer
      Manchester Regenerative Medicine Network Seminar 2018 (Manchester)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 概日リズムと生涯健康医学2018

    • Author(s)
      八木田和弘
    • Organizer
      第46回臨床神経病理懇話会・第18回日本神経病理学会近畿地方会 (京都)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 哺乳類における概日時間秩序の創出機構2018

    • Author(s)
      八木田和弘
    • Organizer
      第25回日本時間生物学会学術大会 (長崎)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 認知症の発症の兆候の検出を補助するための検出補助方法、検出補助装置、検出補助プログラムおよび検出補助システム2020

    • Inventor(s)
      八木田和弘
    • Industrial Property Rights Holder
      八木田和弘
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-008252
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 被検者の概日リズムの質を解析するための解析装置、解析方法、及び解析プログラム2020

    • Inventor(s)
      八木田和弘、小池宣也、笹脇ゆふ
    • Industrial Property Rights Holder
      八木田和弘、小池宣也、笹脇ゆふ
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-001351
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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