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Development of technologies for maintaining undifferentiated state and inducing growth and differentiation of human iPS cell by using chimeric receptor

Research Project

Project/Area Number 24360337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionThe University of Tokyo

Principal Investigator

NAGAMUNE Teruyuki  東京大学, 工学(系)研究科(研究院), 教授 (20124373)

Co-Investigator(Renkei-kenkyūsha) KAWAHARA Masahiro  東京大学, 大学院工学系研究科, 講師 (50345097)
YAMAGUCHI Satoshi  東京大学, 先端科学技術研究センター, 講師 (80398106)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywordsサイトカイン受容体 / キメラ蛋白質 / シグナル伝達 / 未分化維持技術 / 増殖・分化技術 / iPS細胞 / キメラ受容体
Outline of Final Research Achievements

To realize regenerative medicine, a technology to efficiently prepare a large number of differentiated cells of interest at low cost is necessary. However, differentiation-inducing factors such as cytokines are generally expensive. In this study, we designed chimeric receptors, in which the extracellular domain of cytokine receptors is replaced by single-chain antibody, which enables signaling in response to a cheap antigen instead of expensive cytokines. We aimed to develop a system to keep and expand stem cells in an undifferentiated state, and to differentiate them into specific lineages by expressing the cheap antigen-responsive chimeric receptors on the cell surface.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (47 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (33 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] S-Fms signalobody enhances myeloid cell growth and migration2014

    • Author(s)
      Kawahara M et al
    • Journal Title

      Biotechnol. J.

      Volume: 9 Issue: 7 Pages: 954-961

    • DOI

      10.1002/biot.201300346

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Antigen-responsive regulation of cell motility and migration via the signalobodies based on c-Fms and c-Mpl2014

    • Author(s)
      Kawahara M et al
    • Journal Title

      Biotechnol. Prog.

      Volume: 30 Issue: 2 Pages: 411-417

    • DOI

      10.1002/btpr.1861

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Collagen Surfaces Modified with Photo-Cleavable Polyethylene Glycol-Lipid Support Versatile Single-Cell Arrays of Both Non-adherent and Adherent Cells2014

    • Author(s)
      Yamahira S et al
    • Journal Title

      Macromolecular Bioscience

      Volume: 14 Issue: 12 Pages: 1670-1676

    • DOI

      10.1002/mabi.201400312

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Top-down motif engineering of a cytokine receptor for directing ex vivo expansion of hematopoietic stem cells.2013

    • Author(s)
      Saka K, Kawahara M, Teng J, Otsu M, Nakauchi H, Nagamune T.
    • Journal Title

      J Biotechnol.

      Volume: 168 Issue: 4 Pages: 659-65

    • DOI

      10.1016/j.jbiotec.2013.09.012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of unnatural heterodimeric receptors based on IL-2 and IL-6 receptor subunits2013

    • Author(s)
      Ogawa K et al
    • Journal Title

      Biotechnol. Prog.

      Volume: 29 Issue: 6 Pages: 1512-1518

    • DOI

      10.1002/btpr.1785

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies2013

    • Author(s)
      Tone Y et al
    • Journal Title

      Biotechnol. Bioeng.

      Volume: 110 Issue: 12 Pages: 3219-3226

    • DOI

      10.1002/bit.24985

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution of a cytokine receptor scaffold utilizing multiple different tyrosine motifs2013

    • Author(s)
      Saka K et al
    • Journal Title

      Biotechnol. Bioeng.

      Volume: 110 Issue: 12 Pages: 3197-3204

    • DOI

      10.1002/bit.24973

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of antibody/insulin receptor chimera for growth induction of mammalian cells2013

    • Author(s)
      Nakabayashi H et al
    • Journal Title

      Cytotechnology

      Volume: 65 Issue: 6 Pages: 945-953

    • DOI

      10.1007/s10616-013-9571-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Death signalobody: Inducing conditional cell death in response to a specific antigen2013

    • Author(s)
      Tone Y et al
    • Journal Title

      Hum. Gene Ther. Methods

      Volume: 24 Issue: 3 Pages: 141-150

    • DOI

      10.1089/hgtb.2012.147

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of cellular phenotype during in vitro immunization of murine splenocytes for generating antigen-specific immunoglobulin.2013

    • Author(s)
      Inagaki, T., Yoshimi, T., Kobayashi, S., Kawahara, M., and Nagamune, T.
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 115 Issue: 3 Pages: 339-345

    • DOI

      10.1016/j.jbiosc.2012.10.008

    • NAID

      110009596111

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth control ofgenetically modified cells using anantibody/c-Kit chimera2012

    • Author(s)
      Kaneko, E., Kawahara, M., Ueda, H., andNagamune, T.
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 113 Issue: 5 Pages: 641-646

    • DOI

      10.1016/j.jbiosc.2011.12.005

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of target signal transducers utilizing chimeric receptors with signaling-molecule binding motifs2012

    • Author(s)
      Saka K et al
    • Journal Title

      Biotechnol. Bioeng.

      Volume: 109 Issue: 6 Pages: 1528-1537

    • DOI

      10.1002/bit.24421

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering of mammalian cell membrane proteins2012

    • Author(s)
      Kawahara M, et al
    • Journal Title

      Curr. Opin. Chen Eng.

      Volume: 1 Pages: 411-417

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] キメラ受容体を用いた骨髄系前駆細胞株32Dcl3の顆粒球分化誘導2015

    • Author(s)
      沈 鐘楚子ら
    • Organizer
      化学工学会第80年会
    • Place of Presentation
      芝浦工業大学(東京都)
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 光分解性PEG脂質修飾コラーゲン表面を用いた一細胞アレイ作製と定量的イメージサイトメトリー2015

    • Author(s)
      山平真也ら
    • Organizer
      細胞アッセイ研究会
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      2015-01-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 造血幹細胞の増幅を指向したキメラ受容体の構築2014

    • Author(s)
      河原 正浩ら
    • Organizer
      化学工学会第46回秋季大会
    • Place of Presentation
      九州大学(福岡県)
    • Year and Date
      2014-09-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗原応答性キメラ受容体を用いた骨髄性前駆細胞株の増殖・分化制御2014

    • Author(s)
      沈 鐘楚子ら
    • Organizer
      化学工学会第46回秋季大会
    • Place of Presentation
      九州大学(福岡県)
    • Year and Date
      2014-09-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗原応答性キメラ受容体の破骨細胞分化への応用2014

    • Author(s)
      中林 秀人ら
    • Organizer
      化学工学会第46回秋季大会
    • Place of Presentation
      九州大学(福岡県)
    • Year and Date
      2014-09-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] キメラ受容体を用いたタンパク質問相互作用検出法の開発2013

    • Author(s)
      間部 悟, ら
    • Organizer
      化学工学会第78年会
    • Place of Presentation
      大阪大学(大阪府)
    • Year and Date
      2013-03-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗体/インスリン受容体キメラによるインスリンシグナルの活性化2013

    • Author(s)
      中林秀人, ら
    • Organizer
      化学工学会第78年会
    • Place of Presentation
      大阪大学(大阪府)
    • Year and Date
      2013-03-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗原依存的に細胞死シグナルを伝達する抗体/受容体キメラの創製2012

    • Author(s)
      河原正浩, ら
    • Organizer
      第85回生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] キメラ受容体を用いたインフラマソーム活性化因子の探索2012

    • Author(s)
      本田信吾, ら
    • Organizer
      第85回生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] 接着斑キナーゼを利用したタンパク質問相互作用検出系の構築2012

    • Author(s)
      MA YIDAN, ら
    • Organizer
      第85回生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] A novel suicide switch utilizing an antigen-antibody system2012

    • Author(s)
      Masahiro Kawahara, ら
    • Organizer
      JAACT2012
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2012-11-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] nstruetion of Antibody/insulin Receptor Chimera for Mimicking Insulin Receptor Signal2012

    • Author(s)
      Hideto Nakabayashi, ら
    • Organizer
      JAACT2012
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2012-11-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] Design of chimeric receptors to activate target signaling molecules in an antigen-dependent manner2012

    • Author(s)
      Masahiro Kawahara, ら
    • Organizer
      YABEC2012
    • Place of Presentation
      徳島大学(徳島県)
    • Year and Date
      2012-10-27
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗体-Fasキメラを用いたがん細胞の細胞死誘導2012

    • Author(s)
      戸根悠一郎, ら
    • Organizer
      第64回日本生物工学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞増殖を指標とした抗狂犬病ウイルスP蛋白質細胞内抗体の直接選択2012

    • Author(s)
      李松熹, ら
    • Organizer
      第64回日本生物工学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] キメラ受容体を用いた抗フルオレセイン-本鎖抗体のライブラリー選択2012

    • Author(s)
      吉田理恵, ら
    • Organizer
      第64回日本生物工学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 受容体の再構成を通じた細胞内シグナル伝達機構の解明2012

    • Author(s)
      坂 晃一郎, ら
    • Organizer
      第64回日本生物工学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞内シグナル伝達のカスタム設計2012

    • Author(s)
      河原 正浩, ら
    • Organizer
      化学工学会 第44回秋季大会
    • Place of Presentation
      東北大学(宮城県)
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] タンパク質間相互作用検出を目指したキメラ受容体の構築2012

    • Author(s)
      間部 悟, ら
    • Organizer
      化学工学会第44回秋季大会
    • Place of Presentation
      東北大学(宮城県)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 増殖型と死誘導型キメラ受容体を組み合わせた細胞内抗体選択法の開発2012

    • Author(s)
      グエン トゥイズオン, ら
    • Organizer
      化学工学会第44回秋季大会
    • Place of Presentation
      東北大学(宮城県)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 細胞増殖を指標としたタンパク質間相互作用探索法の開発

    • Author(s)
      間部 悟ら
    • Organizer
      第65回日本生物工学会大会
    • Place of Presentation
      広島国際会議場(広島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 増殖誘導型キメラ受容体を用いた狂犬病ウィルス核タンパク質に対するイントラボディ選択

    • Author(s)
      グエン トゥイズオンら
    • Organizer
      第65回日本生物工学会大会
    • Place of Presentation
      広島国際会議場(広島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胚性幹細胞の低コスト分化法開発を志向した抗体/受容体キメラの構築

    • Author(s)
      中林 秀人ら
    • Organizer
      第65回日本生物工学会大会
    • Place of Presentation
      広島国際会議場(広島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 接着斑キナーゼを用いた蛋白質間相互作用の検出

    • Author(s)
      河原 正浩ら
    • Organizer
      第65回日本生物工学会大会
    • Place of Presentation
      広島国際会議場(広島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗体/受容体キメラを用いた増殖から死への細胞運命変換

    • Author(s)
      河原 正浩ら
    • Organizer
      第26回 日本動物細胞工学会2013年度大会 (JAACT2013)
    • Place of Presentation
      ホテルフジタ福井(福井県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗体/インスリン受容体キメラによる細胞の代謝・分化制御

    • Author(s)
      中林 秀人ら
    • Organizer
      第26回 日本動物細胞工学会2013年度大会 (JAACT2013)
    • Place of Presentation
      ホテルフジタ福井(福井県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗体/受容体ハイブリッド分子を用いた抗体選択法の開発

    • Author(s)
      河原 正浩ら
    • Organizer
      化学工学会 第45回秋季大会
    • Place of Presentation
      岡山大学(岡山県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 古典的MAPキナーゼ経路の特異的活性化を指向した人工受容体の構築

    • Author(s)
      石塚 周太ら
    • Organizer
      化学工学会 第45回秋季大会
    • Place of Presentation
      岡山大学(岡山県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ErbB2/受容体キメラと二量体化抗体を利用した抗ErbB2抗体の選択

    • Author(s)
      三浦 知啓ら
    • Organizer
      化学工学会 第45回秋季大会
    • Place of Presentation
      岡山大学(岡山県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] チロシンモチーフを利用した細胞内シグナル伝達の人為的制御

    • Author(s)
      河原 正浩ら
    • Organizer
      第86回生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Chimeric receptor engineering to control cell fate and its applications

    • Author(s)
      Teruyuki Nagamune and Masahiro Kawahara
    • Organizer
      2013 AIChE Annual Meeting
    • Place of Presentation
      サンフランシスコ ヒルトンホテル(米国)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] チロシンモチーフを用いた受容体シグナルの再構成

    • Author(s)
      河原 正浩ら
    • Organizer
      化学工学会 第79年会
    • Place of Presentation
      岐阜大学(岐阜県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 狂犬病ウイルス核タンパク質に対する細胞内抗体のナイーブライブラリーからの選択

    • Author(s)
      グエン トゥイズオンら
    • Organizer
      化学工学会 第79年会
    • Place of Presentation
      岐阜大学(岐阜県)
    • Related Report
      2013 Annual Research Report
  • [Remarks] Cell Engineering

    • URL

      http://park.itc.u-tokyo.ac.jp/nagamune/research.html

    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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