Robust self-renewal in 129 strain derived ESCs established by Esrrb

• Project/Area Number: 19K06459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kyoto Prefectural University of Medicine (2020-2021); Kanazawa Medical University (2019)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥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)
• 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

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。

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.

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。

Research Products

• [Journal Article] LIFシグナルによる多能性幹細胞の自己複製 (2021)
  • Author(s): 大塚哲
  • Journal Title: Journal of Kyoto Prefectural University of Medicine Volume: 130 Issue: 3 Pages: 193-203
  • DOI: 10.32206/jkpum.130.03.193
  • ISSN: 0023-6012
  • Year and Date: 2021-03-25
  • Peer Reviewed
• [Journal Article] Role of Decorin in Posterior Capsule Opacification and Eye Lens Development (2021)
  • Author(s): Shibata Shinsuke、Shibata Naoko、Ohtsuka Satoshi、Yoshitomi Yasuo、Kiyokawa Etsuko、Yonekura Hideto、Singh Dhirendra P.、Sasaki Hiroshi、Kubo Eri
  • Journal Title: Cells Volume: 10 Issue: 4 Pages: 863-863
  • DOI: 10.3390/cells10040863
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 動物実験施設の新築に際して決めておく基本事項 (2020)
  • Author(s): 大塚哲
  • Journal Title: クリーンテクノロジー Volume: 11 Pages: 61-65
• [Journal Article] 動物実験施設新設に際して（金沢医科大学のケース） (2019)
  • Author(s): 大塚哲
  • Journal Title: 実験動物と環境 Volume: 27 Pages: 31-38
  • NAID: 40021908941
• [Journal Article] Induced 2C Expression and Implantation-Competent Blastocyst-like Cysts from Primed Pluripotent Stem Cells (2019)
  • Author(s): Kime Cody、Kiyonari Hiroshi、Ohtsuka Satoshi、Kohbayashi Eiko、Asahi Michio、Yamanaka Shinya、Takahashi Masayo、Tomoda Kiichiro
  • Journal Title: Stem Cell Reports Volume: 13 Issue: 3 Pages: 485-498
  • DOI: 10.1016/j.stemcr.2019.07.011
  • NAID: 120006888454
  • Peer Reviewed / Open Access
• [Presentation] １２９系統マウス由来ES細胞における安定な自己複製の遺伝的な要因 (2019)
  • Author(s): 大塚哲
  • Organizer: 実験動物技術者協会関東支部 ＲＥＧ部会第20回特別講演会
  • Invited
• [Remarks] 金沢医科大学総合医学研究所動物管理室
  • URL: http://www.kanazawa-med.ac.jp/~souiken/cfc/