Molecular mechanism of interference with iPSC induction

• Project/Area Number: 24615004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: Kyoto University
• Principal Investigator: MASUI Shinji 京都大学, iPS細胞研究所, 講師 (20342850)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: iPS細胞 / マスター転写因子 / ポリコーム / コアネットワーク / ES細胞 / 転写因子 / 初期化 / ダイレクトリプログラミング

Outline of Final Research Achievements

We have previously shown that master transcription factors tend to interfere with dedifferentiation triggered by iPSC induction technique in a given cell type. In this study we sought to elucidate the mechanism of the interference. Overexpression of Yamanaka factors including Oct3/4 repressed genes highly expressed in somatic cells. This repression was thought to be their direct effect, as chromatin immunoprecipitation indicated direct binding of Oct3/4 on genes highly expressed in somatic cells. On the other hand, overexpression of a master transcription factor in somatic cells during iPSC induction inhibited this repression and decreased iPSC induction efficiency. These data indicate that this repression is necessary for iPSC induction, and that the interference can be seen as the antagonism between Yamanaka factors and master transcription factors on genes highly expressed in somatic cells.

Research Products

• [Journal Article] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles. (2013)
  • Author(s): Hikichi T, Matoba R, Ikeda T, Watanabe A, Yamamoto T, Yoshitake S, Tamura-Nakano M, Kimura T, Kamon M, Shimura M, Kawakami K, Okuda A, Okochi H, Inoue T, Suzuki A, Masui S.
  • Journal Title: Proceeding of the National Academy of Sciences of USA Volume: 110 Issue: 16 Pages: 6412-6417
  • DOI: 10.1073/pnas.1220200110
  • NAID: 120005244176
  • Peer Reviewed
• [Presentation] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles (2014)
  • Author(s): Masui S
  • Organizer: 47th Annual Meeting for the Japanese Society of Developmental Biologists (JSDB) cosponsored by the Asia-Pacific Developmental Biology Network (APDBN)
  • Place of Presentation: 名古屋市
  • Year and Date: 2014-05-29
• [Presentation] 初期化を阻害する因子が分化を促進する (2014)
  • Author(s): 升井 伸治
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館、京都市
  • Invited
• [Presentation] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles (2013)
  • Author(s): Shinji Masui
  • Organizer: ISSCR 10th annual meeting
  • Place of Presentation: Boston, USA
• [Presentation] 初期化を阻害する因子が分化を促進する (2013)
  • Author(s): 升井 伸治
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド、神戸市
• [Remarks] 京都大学iPS細胞研究所 CiRA（サイラ）
  • URL: http://www.cira.kyoto-u.ac.jp/j/index.html
• [Remarks] 升井研究室
  • URL: http://www.cira.kyoto-u.ac.jp/masui/index.html