| Project/Area Number |
19K06459
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Kyoto Prefectural University of Medicine (2020-2021)
Kanazawa Medical University (2019) |
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Principal Investigator |
OHTSUKA SATOSHI 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (40360515)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ES細胞 / LIFシグナル / Esrrb / Stat3 / 自己複製 / embryonic stem cell / LIF signal / 129 mouse strain / NOD mouse strain |
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| Outline of Research at the Start |
129マウス系統に由来するES細胞の自己複製の頑健性について明らかにする。本研究では、転写因子Esrrbに注目し、その下流遺伝子、Stat3結合能への影響および過剰発現による自己複製の安定化の原因について明らかにする。本研究から、ES細胞の自己複製能の獲得と維持におけるEsrrbの役割が明らかになる。哺乳類由来のナイーブ型多能性幹細胞における自己複製のメカニズム解明のための足がかりとなり、再生医学分野へ貢献できる。
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| Outline of Final Research Achievements |
Mouse embryonic stem cells (mESCs) have been established in conventional serum culture. mESCs derived from 129 mouse strain are stably self-renewing in serum culture. In contrast, mESCs from non-obese diabetic (NOD) mouse strain is not yet maintained in serum culture. In this project, we tried to explore why ESCs from 129 strain were stably established and continued to self-renew in serum culture. We identified transcription factor Esrrb which was specifically retained in 129-ESCs. Maintaining the expression of Esrrb in 2i-established NOD-ESCs allowed self-renewal in an inhibitor-free serum condition. Esrrb enhanced LIF-Stat3 activity in NOD-ESCs at a similar level to that in 129-ESCs. These results indicate that Esrrb supports 129-ESCs self-renewal in serum through enhancing LIF-Stat3 as well as Tfcp2l1 does.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた成果をもとに、ナイーブ型幹細胞の樹立と維持が、ヒトを含む哺乳類からも可能となり、再生医学へ大きく貢献できると考えている。
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