Generation of artificial thymus using trans-differentiation potentials between skin and thymic epithelial cells

• Project/Area Number: 23658246
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Tokyo University of Science
• Principal Investigator: GOITSUKA Ryo 東京理科大学, 生命医科学研究所, 教授 (50301552)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 移植・再生医療 / 再生医学 / 細胞・組織 / 発生・分化 / 免疫学 / 発生•分化 / 胸腺 / 再生 / 転写因子

Research Abstract

Given that it has been demonstrated that thymic epithelial cells have a potential to trans-differentiate into skin epithelial stem cells when exposed to inductive skin microenvironment, these two epithelial cells appears to share similar regulatory mechanisms for stem cell maintenance and differentiation. We sought that there is a possibility to trans-differentiate skin epithelial cells into thymic epithelial cells, eventually to generate the artificial thymus from the skin for regenerative medical application. In the present study, we demonstrated that Meis1, a homeodomain family transcription factor expressed in postnatal thymic epithelial stem cells, is also expressed in skin epithelial stem cells. By applying Meis1 as a marker shared by skin and thymic epithelial stem cells, we may challenge to establish the above-mentioned method to generate the artificial thymus in near future.

Research Products

• [Journal Article] SLP-76 is required for high affinity IgE receptor- and IL-3 receptor-mediated activation of basophils (2012)
  • Author(s): Hidano, S., Kitamura, D., Kumar, L., Geha, R. S., and Goitsuka, R.
  • Journal Title: Int. Immunol.
  • Peer Reviewed
• [Journal Article] Amelioration of collagen-induced arthritis by a novel S1P1antagonist with immunomodulatory activities (2012)
  • Author(s): Fujii, Y., Hirayama, T., Ohtake, T., Ono, N., Inoue, T., Sakurai, T., Takayama, T., Matsumoto, K., Tsukahara, N., Hidano, S., Harima, N., Nakazawa, K., Igarashi, Y., and Goitsuka, R.
  • Journal Title: J. Immunol. Volume: 188(1) Pages: 206-215
  • Peer Reviewed
• [Journal Article] Hypoxia induces CD133 expression in human small cell lung cancer cells by up-regulation of OCT3/4 and SOX2 (2012)
  • Author(s): Iida, H., Suzuki, M., Goitsuka, R., and Ueno, H.
  • Journal Title: Int. J. Oncol. Volume: 40(1) Pages: 71-79
  • Peer Reviewed
• [Journal Article] Lymphopenia induced by a novel selective S1P1 antagonist structurally unrelated to S1P (2012)
  • Author(s): Fujii, Y., Ohtake, H., Ono, N., Hara, T., Sakurai, T., Takahashi, S., Takayama, T., Fukasawa, Y., Shiozawa, F., Tsukahara, N., Hirayama, T., Igarashi, Y., and Goitsuka, R.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1821(4) Pages: 600-606
  • Peer Reviewed
• [Journal Article] Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis (2012)
  • Author(s): Fujii, Y., Ueda, Y., Ohtake, H., Ono, N., Takayama, T., Nakazawa, K., Igarashi, Y. and Goitsuka, R.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 419 (4) Pages: 754-760
  • Peer Reviewed
• [Journal Article] Hypoxia induces CD133 expression in human small cell lung cancer cells by up-regulation of OCT3/4 and SOX2. (2012)
  • Author(s): Iida, H
  • Journal Title: Int. J. Oncol. Volume: 40 Pages: 71-79
  • Peer Reviewed
• [Journal Article] Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities. (2012)
  • Author(s): Fujii, Y.
  • Journal Title: J. Immunol. Volume: 188 Pages: 206-215
  • Peer Reviewed
• [Journal Article] Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis. (2012)
  • Author(s): Fujii, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 419 Pages: 754-760
  • Peer Reviewed
• [Journal Article] Lymphopenia induced by a novel selective S1P1 antagonist structurally unrelated to S1P. (2012)
  • Author(s): Fujii, Y.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1821 Pages: 600-606
  • Peer Reviewed
• [Journal Article] SLP-76 is required for high affinity IgE receptor- and IL-3 receptor-mediated activation of basophils. (2012)
  • Author(s): Hidano, S
  • Journal Title: Int. Immunol. Volume: 24 Pages: 719-727
  • Peer Reviewed
• [Journal Article] Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities. (2012)
  • Author(s): Fujii, Y., Hirayama, T., Ohtake, T., Ono, N., Inoue, T., Sakurai, T., Takayama, T., Matsumoto, K., Tsukahara, N., Hidano, S., Harima, N., Nakazawa, K., Igarashi, Y., and Goitsuka, R
  • Journal Title: J. Immunol Volume: 188 Pages: 206-215
  • Peer Reviewed
• [Journal Article] 胸腺上皮細胞の分化と転写因子 (2011)
  • Author(s): 平山雄啓、後飯塚僚
  • Journal Title: 臨床免疫・アレルギー科 Volume: 第56巻第3号 Pages: 262-268
• [Journal Article] 消滅する免疫系器官としての胸腺:その維持と再生の制御機構 (2011)
  • Author(s): 後飯塚僚
  • Journal Title: 日生研たより Volume: 第57巻第6号 Pages: 78-85
• [Journal Article] 胸腺上皮細胞の分化と転写因子 (2011)
  • Author(s): 平山雄啓、後飯塚僚
  • Journal Title: 臨床免疫アレルギー科 Volume: 第56巻 Pages: 262-268
• [Journal Article] 消滅する器官としての胸腺：胸腺微小環境の形成・恒常性維持の転写制御機構 (2011)
  • Author(s): 後飯塚僚
  • Journal Title: NIBS letter Volume: 第57巻 Pages: 78-85
• [Presentation] Homeodomain transcription factor pKnox1 positively regulates proliferation and survival of c-Kit-positive spermatogonial cells (2012)
  • Author(s): Yasuhiro Kawai, and Ryo Goitsuka
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] T cell egress from the thymus is regulated by the transcriptional coactivator Yap1 expressed in thymic epithelial cells (2012)
  • Author(s): Takehiro Hirayama and Ryo Goitsuka
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 胸腺上皮細胞における転写活性化因子Yap1の機能 (2012)
  • Author(s): 平山雄啓、後飯塚僚
  • Organizer: 第22回Kyoto T Cell Conference (KTCC)
  • Place of Presentation: 京都
• [Presentation] 胸腺上皮細胞における転写活性化因子Yap1の機能 (2012)
  • Author(s): 平山雄啓
  • Organizer: 第22回 Kyoto T Cell Conference
  • Place of Presentation: 京都
• [Presentation] マウス皮膚正常幹細胞におけるMeis1の機能解析 (2011)
  • Author(s): 奥村 和弘,佐藤 美穂,廣瀬 哲史,後飯塚 僚,中村 卓郎,若林 雄一
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Homeodomain transcription factor pKnox1 is required for the differentiation of spermatogonial stem cells (2011)
  • Author(s): Yasuhiro Kawai, Yoshimi Aiyama, Yoshiakira Kanai, Ryo Goitsuka
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Subcellular localization of transcriptional coactivator Yap1, a target of the Hippo pathway, in thymic epithelial cells is regulated by interaction with thymocytes (2011)
  • Author(s): Takehiro Hirayama, Narutochi Tsukahara, and Ryo Goitsuka
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] 卵子形成過程におけるホメオドメイン転写因子pKnox1 の発現と機能 (2011)
  • Author(s): 河合 康洋, 小池 紘子, 青木 悠亮, 後飯 塚僚
  • Organizer: 第104回日本繁殖学会
  • Place of Presentation: 盛岡
• [Presentation] 未知のリガンド・レセプターシステムを介した胸腺細胞・胸腺上皮細胞間のクロストーク機構 (2011)
  • Author(s): 平山雄啓、後飯塚僚
  • Organizer: 第21回Kyoto T Cell Conference (KTCC)
  • Place of Presentation: 京都
• [Presentation] 未知のリガンド・レセプターシステムを介した胸腺細胞・胸腺上皮細胞間のクロストーク機構 (2011)
  • Author(s): 平山雄啓、後飯塚僚
  • Organizer: 第21回 Kyoto T Cell Conference (KTCC)
  • Place of Presentation: 京都
• [Presentation] 卵子形成過程におけるホメオドメイン転写因子pKnox1の発現と機能 (2011)
  • Author(s): 河合 康洋, 小池 紘子, 青木 悠亮, 後飯塚僚
  • Organizer: 第104回日本繁殖学会
  • Place of Presentation: 盛岡
• [Presentation] Subcellular localization of transcriptional coactivator Yap1, a target of the Hippo pathway, in thymic epithelial cells is regulated by interaction with thymocytes. (2011)
  • Author(s): Takehiro Hirayama, Narutochi Tsukahara, and Ryo Goitsuka
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Homeodomain transcription factor pKnox1 is required for the differentiation of spermatogonial stem cells. (2011)
  • Author(s): Yasuhiro Kawai, Yoshimi Aiyama, Yoshiakira Kanai, Ryo Goitsuka
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜