Identification of a nwe factor to promote human iPS cell generation

• Project/Area Number: 24792197
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Gifu University
• Principal Investigator: TAMAOKI Naritaka 岐阜大学, 医学(系)研究科(研究院), 助教 (40585303)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 歯髄細胞 / iPS細胞 / 誘導効率 / DLX4 / TGF-ｂ / 歯髄細胞（DPC） / Dlx4

Outline of Final Research Achievements

In this study, we showed that the reprogramming potential of human dental pulp cells (DPCs) obtained from immature teeth is much higher than those of mature teeth DPCs. Furthermore, immature teeth DPCs can be reprogrammed by OCT3/4 and SOX2, conversely these two factors are insufficient to convert mature teeth DPCs to pluripotent states. Using a gene expression profiles between these two DPC groups, we identified a new transcript factor, distal-less homeobox 4 (DLX4), which was highly expressed in immature teeth DPCs and significantly promoted human iPSC generation in combination with OCT3/4, SOX2, and KLF4. We further show that activation of TGF-b signaling suppresses the expression of DLX4 in DPCs and impairs the iPSC generation of DPCs. Our findings indicate that DLX4 can functionally replace c-MYC and supports efficient reprogramming of immature teeth DPCs.

Research Products

• [Journal Article] The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells (2014)
  • Author(s): Naritaka Tamaoki, Kazutoshi Takahashi, Hitomi Aoki, Kazuki Iida, Tomoko Kawaguchi, Daijirou Hatakeyama, Masatoshi Inden, Naoyuki Chosa, Akira Ishisaki, Takahiro Kunisada, Toshiyuki Shibata, Naoki Goshima, Shinya Yamanaka, and Ken-ichi Tezuka
  • Journal Title: Scientific Reports Volume: なし Issue: 1 Pages: 7283-7283
  • DOI: 10.1038/srep07283
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells (2014)
  • Author(s): Naritaka Tamaoki, Kazutoshi Takahashi, Hitomi Aoki, Kazuki Iida, Tomoko Kawaguchi, Daijirou Hatakeyama, Masatoshi Inden, Naoyuki Chosa, Akira Ishisaki, Takahiro Kunisada, Toshiyuki Shibata, Naoki Goshima, Shinya Yamanaka, and Ken-ichi Tezuka
  • Organizer: アメリカ骨代謝学会
  • Place of Presentation: テキサス州、ヒューストン
  • Year and Date: 2014-09-12 – 2014-09-16
• [Presentation] ホメオボックス遺伝子DLX4はヒトiPS細胞の誘導効率を促進する (2014)
  • Author(s): ○玉置 也剛、青木 仁美、飯田 一規、川口 知子、位田 雅俊、高橋 和利、帖佐 直幸、石崎 明、國貞 隆弘、柴田 敏之、五島 直樹、手塚 建一
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京都国際会議場
• [Presentation] 歯髄細胞株間におけるiPS細胞への誘導効率の比較検討 (2013)
  • Author(s): ○玉置也剛・川口知子・飯田一規・杉山 健・ 畠山大二郎・柴田敏之
  • Organizer: 日本口腔外科学会
  • Place of Presentation: 福岡国際会議場
• [Patent(Industrial Property Rights)] 人工多能性幹細胞の作製方法 (2014)
  • Inventor(s): 手塚 建一、玉置 也剛、国貞 隆弘、柴田 敏之、五島 直樹
  • Industrial Property Rights Holder: 手塚 建一、玉置 也剛、国貞 隆弘、柴田 敏之、五島 直樹
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-26
  • Overseas