Functional development of circadian regulation system

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02600
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kyoto 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
• 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

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).

Free Research Field

環境生理学

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。