Tfcp2l1 confers robust self-renewal in embryonic stem cell

• Project/Area Number: 16K07104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kanazawa Medical University
• Principal Investigator: OHTSUKA Satoshi 金沢医科大学, 総合医学研究所, 准教授 (40360515)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Tfcp2l1 / ES細胞 / LIFシグナル / マウス系統差 / マウス系統 / 多能性 / 胚性幹細胞 / Stat3 / シグナル伝達 / 再生医学 / 幹細胞

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 Tfcp21 which was specifically retained in 129-ESCs. Maintaining the expression of Tfcp21l in 2i-established NOD-ESCs allowed self-renewal in an inhibitor-free serum condition. Tfcp2l1 enhanced LIF-Stat3 activity in NOD-ESCs at a similar level to that in 129-ESCs. These results indicate that Tfcp2l1 supports 129-ESCs self-renewal in serum through enhancing LIF-Stat3.

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] Overlapping function of klf family targets multiple transcription factors to maintain naive pluripotency of ES cells (2018)
  • Author(s): Yamane Mariko、Ohtsuka Satoshi、Matsuura Kumi、Nakamura Akira、Niwa Hitoshi
  • Journal Title: Development Volume: 印刷中 Issue: 10
  • DOI: 10.1242/dev.162404
  • Peer Reviewed
• [Journal Article] The evolutionally-conserved function of group B1 Sox family members confers the unique role of Sox2 in mouse ES cells (2016)
  • Author(s): 2.Niwa, H., Nakamura, A., Urata, M., Shirae-Kurabayashi, M., Kuraku, S. and Ohtsuka, S.
  • Journal Title: BMC Evol. Biol. Volume: 16 Issue: 1 Pages: 173-173
  • DOI: 10.1186/s12862-016-0755-4
  • Peer Reviewed / Open Access
• [Presentation] マウスES細胞における自己複製の安定性とSocs3発現量の相関 (2018)
  • Author(s): 大塚哲
  • Organizer: 第65回実験動物学会総会
• [Presentation] ES cells derivation affected by the genetic background and culture context (2018)
  • Author(s): 大塚哲
  • Organizer: 第41回日本分子生物学会
• [Presentation] マウス ES細胞における自己複製の安定性とSocs3発現量の相関 (2018)
  • Author(s): 大塚哲、石垣靖人
  • Organizer: 第６５回日本実験動物学会総会
• [Presentation] 129系統由来マウスES細胞における血清条件下での安定的な自己複製の遺伝的要因 (2016)
  • Author(s): 大塚哲
  • Organizer: 第54回北陸実験動物研究会
  • Place of Presentation: 金沢医科大学（石川県河北郡内灘町）
  • Invited