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Development of Novel Generation of Nutritional Environmental Risk Assessment System Using Human iPS Cells

Research Project

Project/Area Number 18H02154
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38050:Food sciences-related
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)

Co-Investigator(Kenkyū-buntansha) 賈 慧娟  東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (60456324)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsDOHaD / iPS細胞 / アミノ酸 / 膵臓 / 糖尿病 / 妊娠 / DOHAD / ヒトiPS細胞 / メチオニン / マウス / 微量元素 / DoHAD / iPS / 栄養環境 / リスク評価
Outline of Final Research Achievements

Using iPS cells that mimic human development, we aimed to construct a stem cell-based nutritional environment risk assessment battery to quantitatively evaluate the effects of nutrient overload and deficiency on organ formation and function. Using human iPS cells, we found that limiting just one amino acid during pancreatic differentiation inhibits differentiation into pancreatic beta cells, which are insulin-secreting organs. These findings may be the main reason for the risk of offspring developing diabetes due to inadequate caloric intake by the mother. Furthermore, using pregnant mice, we found that restricting a single amino acid for a very limited period causes abnormal glucose metabolism in the pups. These results indicate that the differentiation system of human iPS cells can be used to fully assess the risk of external nutritional environment during fetal life.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発したヒトiPS細胞分化系を用いた栄養環境リスク評価系とマウスを用いた検証手法を利用することで、胎生期の至適栄養環境を探ると共に糖尿病発症リスクを軽減する栄養介入法を見出すことが可能となり、健康寿命延伸研究を進める上での有用なツールとなる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Generation of human induced pluripotent stem cell-derived functional enterocyte-like cells for pharmacokinetic studies2021

    • Author(s)
      Yoshida S, Honjo T, Iino K, Ishibe R, Leo S, Shimada T, Watanabe T, Ishikawa M, Maeda K, Kusuhara H, Shiraki N, Kume S.
    • Journal Title

      Stem Cell Reports

      Volume: 16 Issue: 2 Pages: 295-308

    • DOI

      10.1016/j.stemcr.2020.12.017

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent progress in pancreatic islet cell therapy2021

    • Author(s)
      Sim Z.E, Shiraki N, Kume S
    • Journal Title

      Inflammation and Regeneration

      Volume: 41 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s41232-020-00152-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system2021

    • Author(s)
      Shinohara Marie、Arakawa Hiroshi、Oda Yuuichi、Shiraki Nobuaki、Sugiura Shinji、Nishiuchi Takumi、Satoh Taku、Iino Keita、Leo Sylvia、Kato Yusuke、Araya Karin、Kawanishi Takumi、Nakatsuji Tomoki、Mitsuta Manami、Inamura Kosuke、Goto Tomomi、Shinha Kenta、Nihei Wataru、Komori Kikuo、Sakai Yasuyuki、Kimura Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 5437-5437

    • DOI

      10.1038/s41598-021-84861-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 臓器チップに要求される細胞組織ソースと細胞共用培地2020

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

      細胞

      Volume: 52 Pages: 174-177

    • Related Report
      2020 Annual Research Report
  • [Journal Article] VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet?Induced Stress2020

    • Author(s)
      Sakano Daisuke、Uefune Fumiya、Tokuma Hiraku、Sonoda Yuki、Matsuura Kumi、Takeda Naoki、Nakagata Naomi、Kume Kazuhiko、Shiraki Nobuaki、Kume Shoen
    • Journal Title

      Diabetes

      Volume: 69 Issue: 11 Pages: 26-33

    • DOI

      10.2337/db20-0207

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detailed analysis at a single-cell level of cells undergoing pancreatic differentiation.2020

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

      J Diabetes Investig.

      Volume: 11 Issue: 1 Pages: 20-21

    • DOI

      10.1111/jdi.13140

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 臓器チップに要求される細胞組織ソースと細胞共用培地2020

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

      月刊細胞

      Volume: 52 Pages: 10-13

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Collagen vitrigel promotes hepatocytic differentiation of induced pluripotent stem cells into functional hepatocyte-like cells.2019

    • Author(s)
      Nakai S, Shibata I, Shitamichi T, Yamaguchi H, Takagi N, Inoue T, Nakagawa T, Kiyokawa J, Wakabayashi S, Miyoshi T, Higashi E, Ishida S, Shiraki N, Kume S
    • Journal Title

      Biology Open

      Volume: 8 Pages: 042192-042192

    • DOI

      10.1242/bio.042192

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A culture substratum with net-like polyamide fibers promotes the differentiation of mouse and human pluripotent stem cells to insulin-producing cells2019

    • Author(s)
      Kaitsuka Taku、Kojima Rie、Kawabe Masaaki、Noguchi Hirofumi、Shiraki Nobuaki、Kume Shoen、Tomizawa Kazuhito
    • Journal Title

      Biomedical Materials

      Volume: 14 Issue: 4 Pages: 045019-045019

    • DOI

      10.1088/1748-605x/ab261c

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fetal androgen signaling defects affect pancreatic β-cell mass and function, leading to glucose intolerance in high-fat diet-fed male rats2019

    • Author(s)
      Harada Naoki、Yotsumoto Yusuke、Katsuki Takahiro、Yoda Yasuhiro、Masuda Tatsuya、Nomura Masayuki、Shiraki Nobuaki、Inui Hiroshi、Yamaji Ryoichi
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 317 Issue: 5 Pages: E731-E741

    • DOI

      10.1152/ajpendo.00173.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis2019

    • Author(s)
      Urmi JF, Itoh H, Muramatsu-Kato K, Kohmura-Kobayashi Y, Hariya N, Jain D, Tamura N, Uchida T, Suzuki K, Ogawa Y, Shiraki N, Mochizuki K, Kubota T, Kanayama N.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 17100-17100

    • DOI

      10.1038/s41598-019-52943-7

    • NAID

      120006716649

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] iPS cell elimination in a cell sheet by methionine-free and 42 °C condition for tumor prevention.2018

    • Author(s)
      Matsuura K, Ito K, Shiraki N, Kume S, Hagiwara N, Shimizu T.
    • Journal Title

      Tissue Eng Part C Methods.

      Volume: 24 Issue: 10 Pages: 605-615

    • DOI

      10.1089/ten.tec.2018.0228

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 吸収腸上皮細胞への分化を促進する低分子化合物のスクリーニング2021

    • Author(s)
      石部隆之介、Sylvia Leo, 渡邊輝彦, 白木伸明、粂 昭苑
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] コラーゲンビトリゲル膜と新規培地で培養したヒトiPS細胞由来小腸細胞の有用性2021

    • Author(s)
      渡邊輝彦, 石川晶也, 石部隆之介, 加藤裕介, 白木 伸明, 粂 昭苑
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 薬物動態評価モデルとしてのヒトiPS細胞由来小腸上皮細胞の開発2021

    • Author(s)
      吉田晋平、本荘貴之、飯生啓太、石部隆之介、Sylvia Leo、嶋田智花、渡邊輝彦、石川昌也、前田和哉、楠原洋之、白木伸明、粂昭苑
    • Organizer
      第5回トランスポーター研究会関東部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト肝細胞の接着性向上とMPSへの応用2021

    • Author(s)
      白木伸明
    • Organizer
      細胞アッセイ研究会シンポジウム 細胞アッセイ技術の現状と将来
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Efficient Generation of Human iPS Cell-derived Pancreatic Beta Cells Using Microcarriers2020

    • Author(s)
      Jason Chng Yhongsheng、Nobuaki Shiraki、Shoen Kume
    • Organizer
      The 19th Congress of the Japanese Society for Regenerative Medicine
    • Related Report
      2019 Annual Research Report
  • [Presentation] iPS細胞肝臓分化誘導系を用いたDOHaDの検証2019

    • Author(s)
      五日市実侑、白木伸明、伊東宏晃、粂 昭苑
    • Organizer
      第8回日本DOHaD学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 薬物動態評価モデルとしてのヒトiPS細胞由来小腸上皮細胞の開発2019

    • Author(s)
      吉田晋平、飯生啓太、石部隆之介、渡邊輝彦、石川晶也、白木伸明、粂 昭苑
    • Organizer
      日本動物実験代替法学会第32回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Elucidating the signal for intestinal differentiation2019

    • Author(s)
      Leo S, Honjo T, Iino K, Ishibe R, Shiraki N, Kume S
    • Organizer
      日本生化学会関東支部例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] メチオニン除去培地とコラーゲンビトリゲル薄膜を用いて分化誘導したヒト iPS 細胞由来肝臓細胞を利用した薬物毒性試験系の構築2019

    • Author(s)
      柴田 伊真・下道 隆広・渡邊 輝彦・山口 宏之・白木 伸明・粂 昭苑
    • Organizer
      細胞アッセイ研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 二臓器連結モデル型 Microphysiological System を用いた新鮮ヒト肝細胞とヒト iPS 細胞由来腸管上皮細胞の灌流共培養2019

    • Author(s)
      小田 雄一・篠原 満利恵・飯生 啓太・新谷 華梨・進 和美・佐藤 琢・荒川 大・白木 伸明・立野 知世・杉浦 慎治・粂 昭苑・加藤 将夫・金森 敏幸・木村 啓志・酒井 康行
    • Organizer
      細胞アッセイ研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Methionine metabolism regulates ESCs/iPSCs Differentiation2018

    • Author(s)
      Nobuaki Shiraki
    • Organizer
      APNNO 2018 Biennial Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多能性幹細胞の未分化維持や分化におけるアミノ酸の役割の解明2018

    • Author(s)
      白木伸明
    • Organizer
      日本アミノ酸学会第12回学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] メチオニン除去培養によるヒトiPS細胞分化促進の機序解明2018

    • Author(s)
      日比 滉大、秋山 智彦、洪実、白木 伸明、粂 昭苑
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 二臓器連結ー圧力駆動型Microphysiological Systemを用いたヒト肝細胞とヒトiPS細胞由来腸管上皮細胞のリアルタイム灌流共培養2018

    • Author(s)
      小田 雄一・篠原 満利恵・飯生 啓太・新谷 華梨・進 和美・佐藤 琢・荒川 大・白木 伸明・立野 知世・杉浦 慎治・粂 昭苑・加藤 将夫・金森 敏幸・木村 啓志・酒井 康行
    • Organizer
      日本動物実験代替法学会第31回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Insulin supplement is essential in differentiating human induced pluripotent stem cells into pancreatic beta cells2018

    • Author(s)
      Erinn Sim Zixuan, Nobuaki Shiraki, Shoen Kume
    • Organizer
      AOCE 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞から機能的な小腸吸収上皮細胞への新規分化誘導系の構築2018

    • Author(s)
      本荘 貴之, 飯生 啓太, 前田 和哉, 渡邊 輝彦, 石川 晶也 , 楠原 洋之, 白木 伸明 , 粂 昭苑
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-12-28  

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