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Development of a Human Taste-Small Intestine-Brain Correlation Model applying for Nutritional Physiology

Research Project

Project/Area Number 19K22988
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Akutsu Hidenori  国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225)

Co-Investigator(Kenkyū-buntansha) 岩槻 健  東京農業大学, 応用生物科学部, 教授 (50332375)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腸管オルガノイド / iPS細胞 / 腸管栄養 / オルガノイド / 小腸 / 味蕾
Outline of Research at the Start

栄養環境が個体生理のみならず現代の疾病動勢にも深く関与している。栄養生理学的研究からの理解が深まっているが、実験動物や動物代替モデルでの試験系にはまだ課題が多い。本研究では、ヒトiPS細胞から生理高機能性を有する疑似臓器(オルガノイド)作製技術を応用することで、食事、栄養の末梢シグナルから中枢の神経回路の活動を解析可能とする生物モデルを具現化する。現代社会の健康をとりまく環境を背景に、食事・栄養が末梢のシグナルから中枢の神経回路を解析するバイオモデルを構築し、味覚-小腸-脳相関モデルの評価系を通すことで、老化や疾患研究の進展へ貢献する。

Outline of Final Research Achievements

Human iPS cell-derived gut organoids were prepared and their secretory properties were analyzed in culture supernatant. We developed a system that allows ELISA analysis of multiple proteins in 1ml of culture medium supernatant. As a result, GLP-1 secretion was confirmed and DEFA5 expression at the protein level was also observed. The results also suggested the usefulness of DEFA5 as a biomarker. In addition, fluorescent-labeled compounds of sugar, lipid, and protein were prepared, and a system was constructed to visually evaluate their absorption in the mini-intestine. When the components that have an inhibitory effect on carbohydrate absorption were allowed to act on the mini-intestine, it was shown that inhibition of carbohydrate absorption could be confirmed. We were able to construct a model platform for visualization of small intestinal absorption utilizing the mini-intestine.

Translated with www.DeepL.com/Translator (free version)

Academic Significance and Societal Importance of the Research Achievements

栄養環境が個体生理のみならず現代の疾病動勢にも深く関与している。栄養生理学的研究からの理解が深まっているが、実験動物や動物代替モデルでの試験系にはまだ課題が多い。本研究では、ヒトiPS細胞から生理高機能性を有する疑似臓器(オルガノイド)作製技術を応用することで、食事、栄養の末梢シグナルから中枢の神経回路の活動を解析可能とする生物モデルを具現化する。現代社会の健康をとりまく環境を背景に、食事・栄養が末梢のシグナルから中枢の神経回路を解析するバイオモデルを構築し、味覚-小腸-脳相関モデルの評価系を通すことで、老化や疾患研究の進展へ貢献する。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019

All Journal Article (19 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 19 results,  Open Access: 18 results) Presentation (3 results) (of which Invited: 3 results)

  • [Journal Article] Xenogeneic-Free Human Intestinal Organoids for Assessing Intestinal Nutrient Absorption2022

    • Author(s)
      Inoue Makoto、Tanaka Yuichi、Matsushita Sakiko、Shimozaki Yuri、Ayame Hirohito、Akutsu Hidenori
    • Journal Title

      Nutrients

      Volume: 14 Issue: 3 Pages: 438-438

    • DOI

      10.3390/nu14030438

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate2021

    • Author(s)
      Inaba Akihiko、Arinaga Ayane、Tanaka Keisuke、Endo Takaho、Hayatsu Norihito、Okazaki Yasushi、Yamane Takumi、Oishi Yuichi、Imai Hiroo、Iwatsuki Ken
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 15 Pages: 7921-7921

    • DOI

      10.3390/ijms22157921

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ngn3-Positive Cells Arise from Pancreatic Duct Cells2021

    • Author(s)
      Kimura-Nakajima Chiemi、Sakaguchi Kousuke、Hatano Yoshiko、Matsumoto Masahito、Okazaki Yasushi、Tanaka Keisuke、Yamane Takumi、Oishi Yuichi、Kamimoto Kenji、Iwatsuki Ken
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 16 Pages: 8548-8548

    • DOI

      10.3390/ijms22168548

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of an epigenetic signature in human induced pluripotent stem cells using a linear machine learning model.2021

    • Author(s)
      Nishino K, Takasawa K, Okamura K, Arai Y, Sekiya A, Akutsu H, Umezawa A.
    • Journal Title

      Hum Cell

      Volume: 34 Issue: 1 Pages: 99-110

    • DOI

      10.1007/s13577-020-00446-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Pluripotent Stem Cell-Derived Organoids as a Model of Intestinal Xenobiotic Metabolism2021

    • Author(s)
      Sasaki Kengo、Inoue Makoto、Machida Masakazu、Kawasaki Tomoyuki、Tsuruta Satoru、Uchida Hajime、Sakamoto Seisuke、Kasahara Mureo、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      StemJournal

      Volume: 3 Issue: 1 Pages: 1-10

    • DOI

      10.3233/stj-200001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of intestinal chemosensory cells from nonhuman primate organoids2021

    • Author(s)
      Inaba Akihiko、Kumaki Shunsuke、Arinaga Ayane、Tanaka Keisuke、Aihara Eitaro、Yamane Takumi、Oishi Yuichi、Imai Hiroo、Iwatsuki Ken
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 536 Pages: 20-25

    • DOI

      10.1016/j.bbrc.2020.12.044

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The hsa-miR-302 cluster controls ectodermal differentiation of human pluripotent stem cell via repression of DAZAP22020

    • Author(s)
      Sugawara T, Miura T, Kawasaki T, Umezawa A, Akutsu H.
    • Journal Title

      Regen Ther

      Volume: 15 Pages: 1-9

    • DOI

      10.1016/j.reth.2020.03.011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative analysis of enteroendocrine cells and their hormones between mouse intestinal organoids and native tissues2020

    • Author(s)
      Ohki Junko、Sakashita Akihiko、Aihara Eitaro、Inaba Akihiko、Uchiyama Hironobu、Matsumoto Masahito、Ninomiya Yuzo、Yamane Takumi、Oishi Yuichi、Iwatsuki Ken
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 84(5) Issue: 5 Pages: 936-942

    • DOI

      10.1080/09168451.2020.1713043

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptomic features of trophoblast lineage cells derived from human induced pluripotent stem cells treated with BMP 42020

    • Author(s)
      Tsuchida Nanae、Kojima Junya、Fukuda Atsushi、Oda Mayumi、Kawasaki Tomoyuki、Ito Hiroe、Kuji Naoaki、Isaka Keiichi、Nishi Hirotaka、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      Placenta

      Volume: 89 Pages: 20-32

    • DOI

      10.1016/j.placenta.2019.10.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice2020

    • Author(s)
      Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, Aoki R, Isobe Y, Kashihara D, Inoue D, Inaba A, Takamura Y, Taira S, Kumaki S, Watanabe M, Ito M, Nakagawa F, Irie J, Kakuta H, Shinohara M, Iwatsuki K, Tsujimoto G, Ohno H, Arita M, Itoh H, Hase K.
    • Journal Title

      Science

      Volume: 367 Issue: 6481 Pages: 8429-8429

    • DOI

      10.1126/science.aaw8429

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Bitter Taste Receptors in the Intestinal Cells of Non-Human Primates2020

    • Author(s)
      Imai Hiroo、Hakukawa Miho、Hayashi Misa、Iwatsuki Ken、Masuda Katsuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 3 Pages: 902-902

    • DOI

      10.3390/ijms21030902

    • NAID

      120006898178

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of Cellular Adhesion and Proliferation in Human Mesenchymal Stromal Cells by the Direct Addition of Recombinant Collagen I Peptide to the Culture Medium2019

    • Author(s)
      Muraya Koji、Kawasaki Tomoyuki、Yamamoto Takeshi、Akutsu Hidenori
    • Journal Title

      BioResearch Open Access

      Volume: 8 Issue: 1 Pages: 210-218

    • DOI

      10.1089/biores.2019.0012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imprinted X‐chromosome inactivation impacts primitive endoderm differentiation in mouse blastocysts2019

    • Author(s)
      Fukuda Atsushi、Motosugi Nami、Ando Mikiko、Kimura Minoru、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      FEBS Letters

      Volume: 594 Issue: 5 Pages: 913-923

    • DOI

      10.1002/1873-3468.13676

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice2019

    • Author(s)
      Ito C, Akutsu H, Yao R, Yoshida K, Yamatoya K, Mutoh T, Makino T, Aoyama K, Ishikawa H, Kunimoto K, Tsukita S, Noda T, Kikkawa M, Toshimori K.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 14249-14249

    • DOI

      10.1038/s41598-019-50516-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.2019

    • Author(s)
      Ogawa S, Yamada M, Nakamura A, Sugawara T, Nakamura A, Miyajima S, Harada Y, Ooka R, Okawa R, Miyauchi J, Tsumura H, Yoshimura Y, Miyado K, Akutsu H, Tanaka M, Umezawa A, Hamatani T.
    • Journal Title

      Stem Cell Reports

      Volume: 12 Issue: 6 Pages: 1366-1379

    • DOI

      10.1016/j.stemcr.2019.05.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploring trophoblast-specific Tead4 enhancers through chromatin conformation capture assays followed by functional screening2019

    • Author(s)
      Tomikawa Junko、Takada Shuji、Okamura Kohji、Terao Miho、Ogata-Kawata Hiroko、Akutsu Hidenori、Tanaka Satoshi、Hata Kenichiro、Nakabayashi Kazuhiko
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 1 Pages: 278-289

    • DOI

      10.1093/nar/gkz1034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool.2019

    • Author(s)
      Yoshida T, Miyado M, Mikami M, Suzuki E, Kinjo K, Matsubara K, Ogata T, Akutsu H, Kagami M and Fukami M.
    • Journal Title

      Human Reproduction

      Volume: 34 Issue: 9 Pages: 1762-1769

    • DOI

      10.1093/humrep/dez117

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and characterization of Suncus murinus intestinal organoid: a useful tool for studying motilin secretion2019

    • Author(s)
      Takakura Natsumi、Takemi Shota、Kumaki Shunsuke、Matsumoto Mio、Sakai Takafumi、Iwatsuki Ken、Sakata Ichiro
    • Journal Title

      Cell Biology International

      Volume: 44 Issue: 1 Pages: 62-69

    • DOI

      10.1002/cbin.11201

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Reg3β-producing cells using IL-22-stimulated enteroids2019

    • Author(s)
      Sato Mika、Inaba Akihiko、Iwatsuki Ken、Saito Yuki、Tadaishi Miki、Shimizu Makoto、Kobayashi-Hattori Kazuo
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 84 Issue: 3 Pages: 594-597

    • DOI

      10.1080/09168451.2019.1695575

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトES/iPS細胞を用いた機能的臓器(ミニ腸等)の創出2019

    • Author(s)
      阿久津英憲
    • Organizer
      日本補綴歯科学会 第128回学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 次世代臓器オルガノイド「ミニ腸」を使った創薬支援2019

    • Author(s)
      阿久津英憲
    • Organizer
      第1回再生医療産業化展
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ゲノム編集技術による研究と応用の課題2019

    • Author(s)
      阿久津英憲
    • Organizer
      第 31 回日本生命倫理学会年次大会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-07-04   Modified: 2023-01-30  

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