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The verification of the fetal origins of adult disease theory using human iPS cell pancreatic differentiation system

Research Project

Project/Area Number 26461638
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionTokyo Institute of Technology

Principal Investigator

shiraki nobuaki  東京工業大学, 生命理工学院, 准教授 (70448520)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsDOHaD / Barker説 / 生活習慣病胎児期発症説 / iPS / アミノ酸 / 分化 / barker仮説 / 膵臓分化 / 生活習慣病胎児期起源説 / メチオニン代謝 / iPS細胞
Outline of Final Research Achievements

Low birth weight is strongly predictive of lifestyle related disease. Animal study indicated that fetal malnutrition induce fetuses with growth retardation have a decreased beta cell mass, which persists into adulthood and causes glucose intolerance. However, The verification of this malnutrition’s effect on human fetuses was difficult. The aim of this study is checking the effect of fetal malnutrition on human using human iPS cell pancreatic differentiation methods. In this study, I have found that important amino acids which regulate pancreatic differentiation at narrow time windows using novel pancreatic differentiation methods established in this study. As a results of amino acid deprivation during pancreatic endocrine differentiation, the number of pancreatic beta cell is significantly decreased at final stage. These results indicated that iPS cell differentiation systems is useful tools for analysis of fetal origins of adult disease theory.

Report

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

    (41 results)

All 2017 2016 2015 2014 Other

All Journal Article (19 results) (of which Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results) Presentation (20 results) (of which Invited: 12 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Erythropoietin facilitates definitive endodermal differentiation of mouse embryonic stem cells via activation of ERK signaling2017

    • Author(s)
      Kaitsuka T, Kobayashi K, Otsuka W, Kubo T, Hakim F, Wei FY, Shiraki N, Kume S and Tomizawa K
    • Journal Title

      Am. J. of Physiology - Cell Physiology

      Volume: 312 Issue: 5 Pages: C573-C582

    • DOI

      10.1152/ajpcell.00071.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.2017

    • Author(s)
      Koga T, Shiraki N, Yano S, Suico MA, Morino-Koga S, Sato T, Shuto T, Kume S, Kai H
    • Journal Title

      BMC Biotechnology

      Volume: 17 Issue: 1 Pages: 14-14

    • DOI

      10.1186/s12896-017-0331-z

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒトiPS細胞膵臓分化系を用いた生活習慣病胎児期起源説の検証2016

    • Author(s)
      白木伸明
    • Journal Title

      BIO Clinica

      Volume: 31 Pages: 76-78

    • Related Report
      2016 Annual Research Report
  • [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] 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] Analytical & Bioanalytical Speciation of Intracellular Zn , Fe and Cu within both iPS Cells and Differentiated Cells Using HPLC Coupled to ICP-MS2016

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

      Journal of Analytical & Bioanalytical Techniques

      Volume: 7 Issue: 1 Pages: 1-8

    • DOI

      10.4172/2155-9872.1000295

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tsuyama T, Shiraki N, Kume S. Definitive Endoderm Differentiation of Human Embryonic Stem Cells Combined with Selective Elimination of Undifferentiated Cells by Methionine Deprivation2016

    • Author(s)
      Tsuyama T, Shiraki N, Kume S.
    • Journal Title

      Methods Mol Biol.

      Volume: 1341 Pages: 173-80

    • DOI

      10.1007/7651_2015_272

    • ISBN
      9781493929535, 9781493929542
    • Related Report
      2015 Research-status Report
  • [Journal Article] Pancreatic differentiation from murine embryonic stem cells. Methods Mol Biol.2016

    • Author(s)
      Sakano D, Shiraki N, Kuem S
    • Journal Title

      Methods Mol Biol.

      Volume: 1341 Pages: 417-423

    • DOI

      10.1007/7651_2015_217

    • ISBN
      9781493929535, 9781493929542
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hepatic Differentiation from Human Ips Cells Using M15 Cells.2016

    • Author(s)
      Umeda K, Shiraki N, Kume S.
    • Journal Title

      Methods Mol Biol.

      Volume: 1357 Pages: 375-81

    • DOI

      10.1007/7651_2014_146

    • ISBN
      9781493930548, 9781493930555
    • Related Report
      2015 Research-status Report
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 糖尿病の再生医療2015

    • Author(s)
      白木伸明・粂昭苑
    • Journal Title

      医学のあゆみ

      Volume: 252 Pages: 647-653

    • Related Report
      2014 Research-status Report
  • [Journal Article] ES/iPS細胞を用いた内胚葉細胞(膵、肝、小腸)への分化誘導2015

    • Author(s)
      白木伸明・粂昭苑
    • Journal Title

      医学のあゆみ

      Volume: 251 Pages: 1153-1159

    • Related Report
      2014 Research-status Report
  • [Journal Article] Hepatic differentiation from murine and human iPS cells using nanofiber scaffolds2014

    • Author(s)
      Yamazoe T., Shiraki N., Kume S.
    • Journal Title

      Methods Mol Biol.

      Volume: epub Pages: 475-83

    • DOI

      10.1007/7651_2014_138

    • ISBN
      9781493930548, 9781493930555
    • Related Report
      2015 Research-status Report
  • [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 Research-status 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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ES/iPS細胞分化制御におけるアミノ酸代謝2014

    • Author(s)
      白木伸明
    • Journal Title

      アミノ酸研究

      Volume: 8 Pages: 5-10

    • NAID

      40020273981

    • Related Report
      2014 Research-status Report
  • [Presentation] 多能性幹細胞から膵臓β細胞への分化誘導2017

    • Author(s)
      白木伸明
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 幹細胞におけるアミノ酸代謝の役割2016

    • Author(s)
      白木伸明
    • Organizer
      第37回日本トリプトファン研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 未分化iPS細胞および分化過程おける亜鉛の役割2016

    • Author(s)
      古田奈央、荒川哲大、岩畑大悟、白木伸明、粂昭苑
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトiPS細胞におけるメチオニン代謝とヒストン就職の役割2016

    • Author(s)
      神戸梓沙、白木伸明、木村宏、粂昭苑
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多能性幹細胞から膵臓β細胞への分化誘導2016

    • Author(s)
      白木伸明
    • Organizer
      幹細胞の培養法・培養工学のためのコンソーシアム第一回シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 幹細胞の維持および分化におけるメチオニン代謝の役割2016

    • Author(s)
      白木伸明
    • Organizer
      日本農芸化学会平成28 年度関西支部大会
    • Place of Presentation
      滋賀
    • Year and Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞におけるメチオニン代謝の役割2016

    • Author(s)
      白木伸明
    • Organizer
      第4回がんと代謝研究会
    • Place of Presentation
      鹿児島
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
    • 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
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] アミノ酸代謝制御による幹細胞の未分化性維持と分化促進2016

    • Author(s)
      白木伸明
    • Organizer
      JBA "未来へのバイオ技術" 勉強会「幹細胞の創薬利用と産学連携」
    • Place of Presentation
      東京
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 幹細胞分化におけるアミノ酸代謝の役割2015

    • Author(s)
      白木伸明、門馬紗英子、粂昭苑
    • Organizer
      第9回日本アミノ酸学会学術大会
    • Place of Presentation
      滋賀県立大学
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 幹細胞維持と分化におけるメチオニン代謝2015

    • Author(s)
      白木伸明
    • Organizer
      第8回Symphony
    • Place of Presentation
      ホテルメトロポリタンエドモント飯田橋
    • Year and Date
      2015-09-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ES/iPS細胞分化制御におけるアミノ酸代謝2015

    • Author(s)
      白木伸明
    • Organizer
      第96回日本栄養•食糧学会関東支部大会
    • Place of Presentation
      新潟大学農学部
    • Year and Date
      2015-09-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [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2015

    • 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年会シンポジウム
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒトES/iPS細胞の未分化維持と分化におけるメチオニン代謝2015

    • Author(s)
      白木伸明
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒトES/iPS細胞の内胚葉分化における細胞外環境の役割2014

    • Author(s)
      白木伸明
    • Organizer
      第2回細胞凝集研究会
    • Place of Presentation
      アクロス福岡
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 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年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 多能性幹細胞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
      日本アミノ酸学会 第8回学術大会
    • Place of Presentation
      東京農業大学世田谷キャンパス
    • Year and Date
      2014-10-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells2014

    • Author(s)
      Nobuaki Shiraki, Shoen Kume
    • Organizer
      Key Forum: From Stem Cells to Organs
    • Place of Presentation
      Kumamoto City Medical Association Hall
    • Year and Date
      2014-09-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒト多能性幹細胞におけるメチオニン代謝の役割2014

    • Author(s)
      白木伸明
    • Organizer
      第18回アミノ酸セミナー
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells2014

    • Author(s)
      Nobuaki Shiraki, Yasuko Shiraki., Tomonori Tsuyama, Fumiaki Obata, Masayuki Miura, Genta Nagae, Hiroyuki Aburatani, Kazuhiko Kume, Fumio Endo, and Shoen Kume
    • Organizer
      第12回幹細胞シンポジウム
    • Place of Presentation
      九州大学医学部 百年講堂
    • Year and Date
      2014-05-31
    • Related Report
      2014 Research-status Report
  • [Remarks] WEBマガジン「KUMADAI NOW」ES・iPS細胞で臓器を作製し再生医療実現を目指す

    • URL

      http://www.kumamoto-u.ac.jp/daigakujouhou/kouhou/kouhoushi/kumadainow/laboratory/k260711

    • Related Report
      2014 Research-status 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
      国立大学法人 熊本大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-104019
    • Filing Date
      2014-05-20
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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