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Establishment of a new methodology for inducing early embryo-like structures from stem cells

Research Project

Project/Area Number 16H04799
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionKyoto University (2017-2018)
Institute of Physical and Chemical Research (2016)

Principal Investigator

Eiraku Mototsugu  京都大学, ウイルス・再生医科学研究所, 教授 (40415097)

Research Collaborator Takata Nozomu  
Okuda Satoru  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsモルフォゲン / オルガノイド / 幹細胞 / 自己組織化 / 局所シグナル制御 / 形態形成 / 初期発生 / 肢芽形成 / 発生制御 / 局所制御 / パターン形成 / イメージング / 分化制御 / 器官発生
Outline of Final Research Achievements

We have developed a system that can generate artificial substance concentration gradients with high spatial and temporal freedom in organoids culture. Using this system, morphogen factors such as BMP, Wnt, Activin, etc. were locally applied under imaging. As a result, we succeeded in inducing ESC-derived organoids with a primitive streak-like structure. The induced organoids exhibited a structure similar to the early embryo, in which the tissues derived from the three germ layers were orderly positioned. Additionally, it was revealed by calcium imaging and statistical analysis that the future differentiation patterns can be predicted from a pattern of spontaneous intracellular calcium transients in a early differentiating ESC aggregate.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、胚葉体に対して人為的にモルフォゲン勾配を安定的に作用させるための新規技術を確立した。これにより、より複雑な組織構造や分化パターンを持つオルガノイド を形成できる可能性を開いた。また三胚葉由来の組織を同時に一つのオルガノイド中に形成させることにより、より生体の個体発生過程に似た分化様式を再現することができる。今後はヒト多能性幹細胞にも応用することにより、再生医療や創薬スクリーニングの開発に寄与することが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results)

  • [Journal Article] Strain-triggered mechanical feedback in self-organizing optic-cup morphogenesis.2018

    • Author(s)
      Okuda S, Takata N, Hasegawa Y, Kawada M, Inoue Y, Adachi T, Sasai Y, Eiraku M.
    • Journal Title

      Science Advances

      Volume: 4 Issue: 11

    • DOI

      10.1126/sciadv.aau1354

    • NAID

      120006539614

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combining Turing and 3D vertex models reproduces autonomous multicellular morphogenesis with undulation, tubulation, and branching2018

    • Author(s)
      Okuda Satoru、Miura Takashi、Inoue Yasuhiro、Adachi Taiji、Eiraku Mototsugu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41598-018-20678-6

    • NAID

      120006517791

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stem cells and genome editing: approaches to tissue regeneration and regenerative medicine2017

    • Author(s)
      Takata Nozomu、Eiraku Mototsugu
    • Journal Title

      Journal of Human Genetics

      Volume: 63 Issue: 2 Pages: 165-178

    • DOI

      10.1038/s10038-017-0348-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Eye Organoid Approach Identifies Six3 Suppression of R-spondin 2 as a Critical Step in Mouse Neuroretina Differentiation2017

    • Author(s)
      Takata Nozomu、Abbey Deepti、Fiore Luciano、Acosta Sandra、Feng Ruopeng、Gil Hyea Jin、Lavado Alfonso、Geng Xin、Interiano Ashley、Neale Geoffrey、Eiraku Mototsugu、Sasai Yoshiki、Oliver Guillermo
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 6 Pages: 1534-1549

    • DOI

      10.1016/j.celrep.2017.10.041

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism2017

    • Author(s)
      Takata Nozomu、Sakakura Eriko、Eiraku Mototsugu、Kasukawa Takeya、Sasai Yoshiki
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41467-017-01105-2

    • NAID

      120006822510

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contractile actin belt and mesh structures provide the opposite dependence of epithelial stiffness on the spontaneous curvature of constituent cells2017

    • Author(s)
      Okuda Satoru、Unoki Katsuyuki、Eiraku Mototsugu、Tsubota Ken-ichi
    • Journal Title

      Development, Growth & Differentiation

      Volume: 59 Issue: 5 Pages: 455-464

    • DOI

      10.1111/dgd.12373

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells2017

    • Author(s)
      Ohgushi Masatoshi、Minaguchi Maki、Eiraku Mototsugu、Sasai Yoshiki
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 1 Pages: 58-66

    • DOI

      10.1016/j.stemcr.2017.05.003

    • NAID

      120006325118

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of molecular turnover in dynamic deformation of a three-dimensional cellular membrane2017

    • Author(s)
      Okuda Satoru、Eiraku Mototsugu
    • Journal Title

      Biomechanics and Modeling in Mechanobiology

      Volume: 16 Issue: 5 Pages: 1805-1818

    • DOI

      10.1007/s10237-017-0920-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a Three-Dimensional Retinal Tissue from Self-Organizing Human ESC Culture2017

    • Author(s)
      Kuwahara Atsushi、Nakano Tokushige、Eiraku Mototsugu
    • Journal Title

      Methods Mol Biol

      Volume: - Pages: 17-29

    • DOI

      10.1007/978-1-4939-6949-4_2

    • ISBN
      9781493969470, 9781493969494
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Various Telencephalic Regions from Human Embryonic Stem Cells in Three-Dimensional Culture2017

    • Author(s)
      Kadoshima Taisuke、Sakaguchi Hideya、Eiraku Mototsugu
    • Journal Title

      Methods Mol Biol

      Volume: - Pages: 1-16

    • DOI

      10.1007/978-1-4939-6949-4_1

    • ISBN
      9781493969470, 9781493969494
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emergence of dorsal ventral polarity in ESC-derived retinal tissue2016

    • Author(s)
      Hasegawa Y, Takata N, Okuda S, Kawada M, Eiraku M, Sasai Y
    • Journal Title

      Development

      Volume: 143 Issue: 21 Pages: 3895-3906

    • DOI

      10.1242/dev.134601

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Self-organization of patterned functional tissues from pluripotent stem cells2019

    • Author(s)
      Mototsutu Eiraku
    • Organizer
      119th International Titisee Conference:Tissue formation and regeneration: from molecules to models
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 発生システムの試験管内構築と制御2018

    • Author(s)
      永樂元次
    • Organizer
      日本発生生物学会秋季シンポジウム2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Self-organization of patterned tissues from mouse and human stem cells2018

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      EMBO Workshop :Molecular mechanisms of developmental and regenerative biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多能性幹細胞からの神経組織形成~海馬組織の再構成はできるか?~2018

    • Author(s)
      永樂元次
    • Organizer
      第27回 海馬と高次脳機能学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 多細胞の自己組織発生制御によるin vitro での機能的な神経組織形成2018

    • Author(s)
      永樂元次
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Self-organized formation of neural organoids from stem cells2018

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 多細胞体の自己組織的なパターン形成および形態形成メカニズム2018

    • Author(s)
      永樂元次
    • Organizer
      Cell aggregation meeting 2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Self-organization of patterned tissues from mouse and human stem cells2017

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      CDB Symposium 2017
    • Place of Presentation
      RIKEN CDB, Kobe, Japan
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Self-organization of patterned tissues from mouse and human stem cells2017

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      DB Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Self-organization of patterned tissues from mouse and human stem cells2017

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      Cold Spring Harbor Laboratory
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Self-organization of patterned tissues from pluripotent stem cells2016

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      Engineering the embryo beyond systems biology
    • Place of Presentation
      Institut Pasteur, Paris, France
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Self-organization of patterned tissues from pluripotent stem cells2016

    • Author(s)
      Mototsugu Eiraku
    • Organizer
      SDB 75th Annual Meeting/ISD 19th International Conference
    • Place of Presentation
      Marriott Copley Place, Boston, USA
    • Year and Date
      2016-08-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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