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Generation of human iPS-derived pancreatic beta cells and its application towards regenerative medicine

Research Project

Project/Area Number 26253059
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTokyo Institute of Technology

Principal Investigator

Kume Shoen  東京工業大学, 生命理工学院, 教授 (70347011)

Co-Investigator(Kenkyū-buntansha) 荒木 喜美  熊本大学, 学内共同利用施設等, 教授 (90211705)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥41,340,000 (Direct Cost: ¥31,800,000、Indirect Cost: ¥9,540,000)
Fiscal Year 2016: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2015: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Keywords多能性幹細胞 / 分化誘導 / 糖尿病 / 再生医療 / 膵臓 / 代謝 / 増殖 / モノアミン / ドパミン / インスリン / 化合物 / 再生医学 / 膵β細胞 / 膵臓β細胞
Outline of Final Research Achievements

Through screening and analysis of small molecular compound that potentiated differentiation of human induced pluripotent stem (hiPS) cells into pancreatic beta cells, we found that activation of Wnt signal increased beta cell differentiation in hiPS cells, and that our previously identified VMAT2-monoamine as a negative regulator for pancreatic differentiation, also applied to hiPS cells. We also identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist, as a compound that enhances beta cell mass. In adult islet dissociation cultures, beta cell loss occurs through dedifferentiation, which was prevented by DPD. Dopamine modulates beta cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling, a previously identified beta cell mass positive regulator. We believe that our knowledge on regulation of beta cell differentiation and cell mass regulation would be profitable for future manipulation of hiPS-derived beta cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (54 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 11 results,  Acknowledgement Compliant: 7 results) Presentation (32 results) (of which Int'l Joint Research: 6 results,  Invited: 20 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Heterogeneity of beta-cells.2017

    • Author(s)
      Shoen Kume
    • Journal Title

      J Diabetes Investig

      Volume: 印刷中 Issue: 5 Pages: 656-657

    • DOI

      10.1111/jdi.12608

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in expression of C2cd4c in pancreatic endocrine cells during pancreatic development2016

    • Author(s)
      Omori H, Ogaki S, Sakano D, Sato M, Umeda K, , Nakagata N, Kume S
    • Journal Title

      FEBS Lett

      Volume: 590 Issue: 16 Pages: 2584-93

    • DOI

      10.1002/1873-3468.12271

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dopamine D2 receptor-mediated regulation of pancreatic b cell mass.2016

    • Author(s)
      1.Sakano D, Choi S, Kataoka M, Shiraki N, Uesugi M, Kume K, Kume S
    • Journal Title

      Stem Cell Reports

      Volume: 7 Issue: 1 Pages: 95-109

    • DOI

      10.1016/j.stemcr.2016.05.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Late stage definitive endodermal differentiation can be defined by Daf1 expression2016

    • Author(s)
      Ogaki S, Omori H, Morooka M, Shiraki N, Ishida S, Kume S
    • Journal Title

      BMC Dev Biol

      Volume: 16 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12861-016-0120-2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of intracellular Zn, Fe, Cu within both iPS cells and differentiated cells using HPLC coupled to ICP-MS.2016

    • Author(s)
      Arakawa A, Shiraki N, Tsuyama T, Kume S, Iwahata D, Yamada N
    • Journal Title

      J. Anal Bioanal Tech

      Volume: 7 Pages: 1000295-1000295

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporal effects of Notch signaling and potential cooperation with multiple downstream effectors on adenohypophysis cell specification in zebrafish2016

    • Author(s)
      Y. Nakahara, A. Muto, R. Hirabayashi, T. Sakuma, T. Yamamoto, S. Kume, and Y. Kikuchi
    • Journal Title

      Genes to Cells

      Volume: 21 Issue: 5 Pages: 492-504

    • DOI

      10.1111/gtc.12358

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural cells play an inhibitory role in pancreatic differentiation of pluripotent stem cells.2015

    • Author(s)
      Nakashima R, Morooka M, Shiraki N, Sakano D, Ogaki S, Kume K, Kume S
    • Journal Title

      Genes to cells

      Volume: 20 Issue: 12 Pages: 1028-45

    • DOI

      10.1111/gtc.12308

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The NMDA receptor promotes sleep in the fruit fly, Drosophila melanogaster.2015

    • Author(s)
      Tomita, J., Ueno, T., Mitsuyoshi, M., Kume, S. and Kume, K.
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 5 Pages: e0128101-e0128101

    • DOI

      10.1371/journal.pone.0128101

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A cost effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells.2015

    • Author(s)
      Ogaki S, Morooka M, Otera K and Kume S.
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 17297-17297

    • DOI

      10.1038/srep17297

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells.2014

    • Author(s)
      Shiraki, N., Shiraki, Y., Tsuyama, T., Obata, F., Miura, M., Nagae, G., Aburatani, H., Kume, K., Endo, F., and Kume, S.
    • Journal Title

      Cell Metab.

      Volume: 19 Issue: 5 Pages: 780-794

    • DOI

      10.1016/j.cmet.2014.03.017

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] High Oxygen Condition Facilitates the Differentiation of Mouse and Human Pluripotent Stem Cells into Pancreatic Progenitors and Insulin-producing Cells.2014

    • Author(s)
      Farzana Hakim, Taku Kaitsuka, Jamiruddin Mohd. Raeed, Fan-Yan Wei, Nobuaki Shiraki, Tadayuki Akagi, Takashi Yokota, Shoen Kume, and Kazuhito Tomizawa
    • Journal Title

      The journal of biological chemistry

      Volume: 289 Issue: 14 Pages: 9623-9638

    • DOI

      10.1074/jbc.m113.524363

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Beneficial effect of insulin treatment on islet transplantation outcomes in akita mice.2014

    • Author(s)
      Kikawa K, Sakano D, Shiraki N, Tsuyama T, Kume K, Endo F, Kume S.
    • Journal Title

      Plos one

      Volume: 9(4) Issue: 4 Pages: e95451-e95451

    • DOI

      10.1371/journal.pone.0095451

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Profiling of embryonic stem cell differentiation.2014

    • Author(s)
      Shiraki N., Ogaki S and Kume S
    • Journal Title

      The Review of Diabetic Studies

      Volume: 11(1) Issue: 1 Pages: 102-114

    • DOI

      10.1900/rds.2014.11.102

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of insulin-producing beta-like cells from human iPS cells in a defined and completely Xeno-free culture system.2014

    • Author(s)
      Shahjalal HM, Shiraki N, Sakano D, Kikawa H, Ogaki S, Baba H, Kume K., Kume S.
    • Journal Title

      Journal of Molecular Cell Biology

      Volume: 6 Issue: 5 Pages: 394-408

    • DOI

      10.1093/jmcb/mju029

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] VMAT2 identified as a regulator of late-stage beta cell differentiation.2013

    • Author(s)
      Sakano, D., Shiraki, N., Kikawa, K., Yamazoe, T., Kataoka, M., Umeda, K., Araki, K., Mao, D., Matsumoto, S., Nakagata, N., Andersson, O., Stainier, D., Endo, F., Kume, K., Uesugi, M. and Kume, S.
    • Journal Title

      Nat. Chem. Biol.

      Volume: 10 Issue: 2 Pages: 141-148

    • DOI

      10.1038/nchembio.1410

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒトiPS細胞におけるメチオニン代謝とヒストン修飾の役割の解明2016

    • Author(s)
      神戸梓沙、白木伸明、木村宏、粂昭苑
    • Organizer
      分子生物学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] モノアミンによるインスリン分泌制御機構の解明2016

    • Author(s)
      上船史弥、園田雄輝、坂野大介、粂昭苑
    • Organizer
      分子生物学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Generation of insulin-producing β-like cells from human iPS cell2016

    • Author(s)
      Shoen Kume
    • Organizer
      11th IDF WPR & 8th AASD meeting
    • Place of Presentation
      Taipei
    • Year and Date
      2016-10-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Monoamine signaling controls cell proliferation and differentiation state of pancreatic beta cell2016

    • Author(s)
      Daisuke Sakano, Choi Sungik, Masateru Kataoka, Nobuaki Shiraki, Shoen Kum
    • Organizer
      日本生化学会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多能性幹細胞の分化制御と代謝2016

    • Author(s)
      粂昭苑
    • Organizer
      細胞生物学会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Monoamine signals that control differentiation and proliferation of pancreatic beta cells.2016

    • Author(s)
      Shoen Kume
    • Organizer
      CDB symposium
    • Place of Presentation
      神戸
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトiPS細胞由来膵臓細胞を用いた膵臓β細胞分化を促進する化合物の探索2016

    • Author(s)
      白木伸明、師岡茉由 、白濱理絵 、山下智大、粂昭苑
    • Organizer
      日本薬学会135年会
    • Place of Presentation
      神戸
    • Year and Date
      2016-03-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ヒトES/iPS細胞の未分化能維持と分化 におけるメチオニン代謝2016

    • Author(s)
      白木伸明 粂 昭苑
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞から膵β細胞への分化誘導2016

    • Author(s)
      粂昭苑
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた糖尿病の再生治療のアプローチ2016

    • Author(s)
      粂昭苑
    • Organizer
      第43回日本膵・膵島移植研究会
    • Place of Presentation
      広島市
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた糖尿病の再生・創薬研究2016

    • Author(s)
      粂昭苑
    • Organizer
      国立国際医療研究センター 研究所セミナー
    • Place of Presentation
      東京
    • Year and Date
      2016-02-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を使った消化器官の再生医療への取組み2016

    • Author(s)
      粂昭苑
    • Organizer
      第19回再生医療の実用化に関するニーズ発表会
    • Place of Presentation
      神戸
    • Year and Date
      2016-02-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた膵β細胞の再生医療への展望2016

    • Author(s)
      粂昭苑
    • Organizer
      千葉次世代糖尿病治療研究会
    • Place of Presentation
      千葉市
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Pluripotent stem cells for modeling cellular biology, developmental biology and regenerative medicine2016

    • Author(s)
      Shoen Kume
    • Organizer
      第4回の生命理工国際シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] 多能性幹細胞から膵臓β細胞を創る2016

    • Author(s)
      粂 昭苑
    • Organizer
      「細胞を創る」研究会9.0
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Generation of insulin-producing β-like cells from human iPS cells2016

    • Author(s)
      Shoen Kume
    • Organizer
      10th International Conference on Cell Therapy (IRICT)
    • Place of Presentation
      Seoul
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞の未分化維持及び分化におけるメチオニン代謝の役割2016

    • Author(s)
      門馬 紗英子、白木伸明、及川彰、粂昭苑
    • Organizer
      細胞生物学会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多能性幹細胞の多能性維持および分化におけるアミノ酸およびその誘導体の役割2015

    • Author(s)
      粂昭苑
    • Organizer
      BMB2015
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵β細胞の複製を促進する低分子化合物の探索2015

    • Author(s)
      坂野大介・崔 成翼・片岡正光・粂昭苑
    • Organizer
      BMB2015
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] ES/iPS細胞を用いた糖尿病の創薬研究2015

    • Author(s)
      粂昭苑
    • Organizer
      Bio Japan
    • Place of Presentation
      横浜
    • Year and Date
      2015-10-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 多能性幹細胞を用いた膵β細胞の再生治療2015

    • Author(s)
      粂昭苑
    • Organizer
      第15回Islet Biology 研究会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を応用した膵β細胞の再生治療2015

    • Author(s)
      粂昭苑
    • Organizer
      第67回 糖尿病血管障害講演会
    • Place of Presentation
      東京都
    • Year and Date
      2015-06-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた肝と膵の再生医学研究2015

    • Author(s)
      粂昭苑
    • Organizer
      第22回肝細胞研究会
    • Place of Presentation
      米子
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 膵β細胞の複製を促進する低分子化合物の探索2014

    • Author(s)
      坂野大介、崔 成翼、片岡正光、粂昭苑
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト多能性幹細胞の未分化維持および分化におけるメチオニン代謝の役割2014

    • Author(s)
      白木 伸明, 白木 恭子, 津山 友徳, 小幡 史明, 三浦 正幸, 永江 玄太, 油谷 浩幸, 粂 和彦, 遠藤 文夫, 粂 昭苑
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Signals that control differentiation of ES/iPS cells into pancreatic beta cells2014

    • Author(s)
      Shoen Kume
    • Organizer
      The 8th International Conference on Cell Therapy
    • Place of Presentation
      Seoul
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多能性幹細胞モデルを用いた膵臓の発生分化研究2014

    • Author(s)
      粂 昭苑
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS技術を用いた膵β細胞の分化誘導研究2014

    • Author(s)
      粂 昭苑
    • Organizer
      第29回日本糖尿病合併症学会
    • Place of Presentation
      東京都
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells2014

    • Author(s)
      Nobuaki Shiraki and Shoen Kume
    • Organizer
      Key Forum: From Stem Cells to Organs
    • Place of Presentation
      Kumamoto
    • Year and Date
      2014-09-04
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chemical genetic identification of signals that control late-stage pancreatic beta cell differentiation2014

    • Author(s)
      Shoen Kume
    • Organizer
      ISSCR (International Society of Stem Cell Research)
    • Place of Presentation
      Vancouber
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Signals that control differentiation of pluripotent stem cells into pancreatic beta cells2014

    • Author(s)
      Shoen Kume
    • Organizer
      Tissue Engineering Regenerative Medicine International Society (TERMIS-EU 2014)
    • Place of Presentation
      Genova
    • Year and Date
      2014-06-10
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 再生医療を用いた糖尿病治療の今後の展望2014

    • Author(s)
      粂昭苑
    • Organizer
      日本内分泌学会学術総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] 新膵臓病学 第2章膵の発生2017

    • Author(s)
      粂 昭苑
    • Publisher
      南江堂
    • Related Report
      2016 Annual Research Report
  • [Remarks] 研究成果概要 粂・白木研究室

    • URL

      http://www.stem.bio.titech.ac.jp/results.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京工業大学 生命理工学系 News

    • URL

      http://educ.titech.ac.jp/bio/news/2016_07/052422.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 研究室ウエブページの研究紹介

    • URL

      http://www.stem.bio.titech.ac.jp/results.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] インスリン産生細胞の分化誘導方法2015

    • Inventor(s)
      粂 昭苑、白木伸明
    • Industrial Property Rights Holder
      粂 昭苑、白木伸明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アミノ酸組成変更培地を用いた幹細胞の分化促進方法、及び該方法を用いて処理された幹細胞、並びに培地2015

    • Inventor(s)
      粂 昭苑、遠藤文夫、白木伸明、白木恭子、粂 和彦、馬渡一徳
    • Industrial Property Rights Holder
      粂 昭苑、遠藤文夫、白木伸明、白木恭子、粂 和彦、馬渡一徳
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-184294
    • Filing Date
      2015-09-10
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] インスリン産生細胞の分化誘導方法2014

    • Inventor(s)
      粂 昭苑、白木伸明
    • Industrial Property Rights Holder
      粂 昭苑、白木伸明
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-104019
    • Filing Date
      2014-05-20
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-12-17  

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