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Understanding the mechanism of human mesoderm development using heterogeneity of induced mesodermal cells

Research Project

Project/Area Number 17H05006
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Developmental biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Takasato Minoru  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (40788676)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Keywords中胚葉発生 / 腎臓オルガノイド / ヒトiPS細胞 / 分化誘導 / 1細胞解析 / 発生生物学 / 多能性幹細胞 / 分化制御 / 中胚葉 / 1細胞解析
Outline of Final Research Achievements

In this study, we induced mesoderm consisting of heterogeneous cell populations from human iPS cells. To elucidate cell fate determination in mesoderm differentiation, we performed single-cell RNA-seq analysis upon above differentiation system. The results showed that human iPS cells differentiate into paraxial mesoderm, intermediate mesoderm, lateral plate mesoderm, and neural crest cells. We have succeeded in visualizing the process of differentiation and precise timings of fate determination in each mesoderm. Furthermore, the signaling pathways that may act in fate determination in each mesodermal cell were identified by ligand-receptor analysis.

Academic Significance and Societal Importance of the Research Achievements

本研究の完成は、ヒトiPS細胞の分化誘導系を利用してヒトの発生学を行う好例となる。ヒト胎児の研究利用に限界がある中、ヒト発生学の進展に資する点で、学術的な意味を持つ。また、ヒト中胚葉発生のパターニング制御を司る分子メカニズムの理解は、そのパターニングを人工的に制御する手法の開発に有用である。例えば、中胚葉から発生する組織は、腎臓に限らず、心臓、副腎、性線、骨、筋肉、血管、血液、など様々あるが、本研究成果は、これらの組織をヒトiPS細胞から効率良く誘導する分化系の開発に直接的に貢献する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (61 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (56 results) (of which Int'l Joint Research: 13 results,  Invited: 52 results)

  • [Journal Article] Challenges to future regenerative applications using kidney organoids2020

    • Author(s)
      Takasato Minoru、Wymeersch Filip J.
    • Journal Title

      Current Opinion in Biomedical Engineering

      Volume: 13 Pages: 144-151

    • DOI

      10.1016/j.cobme.2020.03.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multivariate patterning of human pluripotent cells under perfusion reveals critical roles of induced paracrine factors in kidney organoid development2020

    • Author(s)
      Glass Nick R.、Takasako Minoru、Er Pei Xuan、Titmarsh Drew M.、Hidalgo Alejandro、Wolvetang Ernst J.、Little Melissa H.、Cooper-White Justin J.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 2 Pages: 2746-2746

    • DOI

      10.1126/sciadv.aaw2746

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 自己組織化を利用したiPS細胞由来腎臓オルガノイド作製2019

    • Author(s)
      高里 実
    • Journal Title

      実験医学別冊 決定版 オルガノイド実験スタンダード

      Volume: 別冊 Pages: 190-200

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 多能性幹細胞から作製する腎臓オルガノイドとその応用2019

    • Author(s)
      谷口 純一, 高里 実
    • Journal Title

      月刊細胞

      Volume: 51 Pages: 163-167

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Evaluation of variability in human kidney organoids2018

    • Author(s)
      Phipson Belinda、Er Pei X.、Combes Alexander N.、Forbes Thomas A.、Howden Sara E.、Zappia Luke、Yen Hsan-Jan、Lawlor Kynan T.、Hale Lorna J.、Sun Jane、Wolvetang Ernst、Takasato Minoru、Oshlack Alicia、Little Melissa H.
    • Journal Title

      Nature Methods

      Volume: 16 Issue: 1 Pages: 79-87

    • DOI

      10.1038/s41592-018-0253-2

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒトiPS細胞を用いた3次元尿路系組織の作製2020

    • Author(s)
      高里 実
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイド研究の進展と社会実装への課題2020

    • Author(s)
      高里 実
    • Organizer
      第28回日本逆流性腎症 フォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドを用いた細胞成熟度多様性の理解と制御2020

    • Author(s)
      高里 実
    • Organizer
      第5回公開シンポジウム「多面的1細胞解析技術が解き明かす細胞社会ダイバーシティー」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドで研究する細胞ダイバーシティとシンギュラリティイベント2020

    • Author(s)
      Takasato M
    • Organizer
      BDR-CiRA Exchange seminar
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドを用いた細胞成熟度多様性の理解と制御2020

    • Author(s)
      高里 実
    • Organizer
      新学術(シンギュラリティ×細胞ダイバース)合同ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓再生実現に向けたin vitroからのアプローチ ~腎臓オルガノイドの構築~2020

    • Author(s)
      高里 実
    • Organizer
      第7回日本腎臓研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 三次元腎臓組織のin vitro構築2019

    • Author(s)
      高里 実
    • Organizer
      第7回 細胞凝集研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS 細胞から作製する腎臓細胞2019

    • Author(s)
      高里 実
    • Organizer
      日本動物実験代替法学会第32回大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 自己組織化を利用した iPS 細胞由来腎臓オルガノイド作製2019

    • Author(s)
      高里 実
    • Organizer
      第3 回 がん三次元培養研究会 「三次元培養に基づくがん精密医療への展開」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 人工MET発生系と機械学習を組み合わせた細胞特異性の同定と解析2019

    • Author(s)
      高里 実
    • Organizer
      理化学研究所 生命機能科学研究センター DECODEセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒト多能性幹細胞から分化誘導した 3 次元腎臓の組織構造と薬物試験への応用2019

    • Author(s)
      高里 実
    • Organizer
      CBI学会2019年大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 上皮-間葉の相互作用による腎臓オルガノイドの作製2019

    • Author(s)
      高里 実
    • Organizer
      2019 年度 生理研研究会 「上皮膜・間質の機能連関と病態発現機構解明のためのストラテジー」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Recreating a whole urinary tract from human pluripotent stem cells2019

    • Author(s)
      Takasato M
    • Organizer
      Renal Division of National Taiwan University of Hospital
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recreating a whole urinary tract from human pluripotent stem cells2019

    • Author(s)
      Takasato M
    • Organizer
      2019 Joint Conference of Taiwanese Society of Developmental Biology and Taiwan Society for Stem Cell Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 3次元腎臓の作製と医療応用への可能性2019

    • Author(s)
      高里 実
    • Organizer
      東京医科歯科大学小児科内 Monday セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Generating the whole urinary tract from hPSCs2019

    • Author(s)
      高里 実
    • Organizer
      RIKEN BDR-CCHMC CuSTOM Joint Workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vitro reconstitution of wolffian duct using human pluripotent stem cells2019

    • Author(s)
      Taniguchi J、Takasato M.
    • Organizer
      ISSCR 2019 annual meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SINGLE-CELL TRANSCRIPTOME APPROACH TO INVESTIGATE THE MECHANISM OF SPECIFING MESODERM LINEAGES USING HUMAN INDUCIBLE PLURIPOTENT STEM CELLS2019

    • Author(s)
      Zhao W、Takasato M
    • Organizer
      ISSCR 2019 annual meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Utilizing kidney organoids as a platform to analyze renal diseases2019

    • Author(s)
      高里 実
    • Organizer
      第62回日本腎臓学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞から作製する腎臓組織2019

    • Author(s)
      高里 実
    • Organizer
      理化学研究所 生体イメージングサイエンスセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Investigating the Niche-Specific Regulation of MET Events within Kidney Organoids2019

    • Author(s)
      高里 実
    • Organizer
      新学術領域「シンギュラリティ生物学」第2回領域会議
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒト多機能性幹細胞を用いた腎臓オルガノイドの作製2019

    • Author(s)
      高里 実
    • Organizer
      第29回日本臨床工学会および2019年度公益社団法人日本臨床工学技士会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Single-cell transcriptome approach to investigate the mechanism of specifying mesoderm lineages using human iPSCs2019

    • Author(s)
      Zhao W、Takasato M
    • Organizer
      日本発生生物学会第52回大会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation of bladder organoids from human iPS cells2019

    • Author(s)
      尾藤 和浩、高里 実
    • Organizer
      2nd JSDB-GfE Young scientist exchange meeting in Kyoto 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generating a functional kidney from human pluripotent stem cells2019

    • Author(s)
      Takasato M
    • Organizer
      State-of-the-Art 3D Tissue Culture & Organoids 2019 at Okinawa Institute of Science and Technology Graduate University
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腎臓再生医療研究はどこまで進んでいるか-iPS細胞からのオルガノイド作製-2018

    • Author(s)
      高里 実
    • Organizer
      第4回生活習慣病とがんの研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵臓由来オルガノイドの樹立培養とISPR/Cas9による表現型解析2018

    • Author(s)
      高里 実
    • Organizer
      循環器オルガノイド研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 一細胞トランスクリプトームによる腎臓オルガノイド成熟化に伴う細胞不均一性の解析2018

    • Author(s)
      佐原 義基、高里 実
    • Organizer
      新学術領域「細胞ダイバース」第2回若手ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 3次元腎臓オルガノイドの 創薬利用への可能性と課題2018

    • Author(s)
      高里 実
    • Organizer
      第6回動物実験代替法検討会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腎臓再生医療はどこまで進んでいるか - iPS細胞からのオルガノイド作製 -2018

    • Author(s)
      高里 実
    • Organizer
      Biological Science Seminar
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 3-D kidney organoids to model renal morphogenesis2018

    • Author(s)
      高里 実
    • Organizer
      Frontiers in Organoid Medicine Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recreating the kidney from human pluripotent stem cells2018

    • Author(s)
      高里 実
    • Organizer
      京都大学大学院 再生医療・臓器再建医学コース
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Recreating a Kidney from Human Pluripotent Stem Cells2018

    • Author(s)
      高里 実
    • Organizer
      2018 International Conference on Cell-Based Clinical Application
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recreating a kidney from human pluripotent stem cells2018

    • Author(s)
      高里 実
    • Organizer
      Workshop on Multi-Cellular Engineered Living Systems
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞からの腎臓再創造2018

    • Author(s)
      高里 実
    • Organizer
      第20回生命科学研究科シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞から作製した腎臓オルガノイド内ダイバーシティ2018

    • Author(s)
      高里 実
    • Organizer
      細胞ダイバース第2回公開シンポジウム「臓器構築システムの解明に向けた細胞社会ダイバーシティー研究の最前線」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイド作成系を利用したヒト腎臓発生機構の1細胞トランスクリプトーム解析2018

    • Author(s)
      高里 実
    • Organizer
      第61回日本腎臓学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来腎臓オルガノイドを用いた腎薬物動態評価系の開発2018

    • Author(s)
      高里 実
    • Organizer
      第25回HAB研究機構学術年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞を用いた腎臓再創造の試み2018

    • Author(s)
      高里 実
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulating the patterning of mesoderm and generating kidney organoids by the directed differentiation of human pluripotent stem cells2017

    • Author(s)
      高里 実
    • Organizer
      CDB-CiRA Joint Retreat
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Generation of kidney tissues from iPS cells2017

    • Author(s)
      高里 実
    • Organizer
      SPIRITS国際シンポジウム2018
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドの応用利用へ向けた課題と取り組み2017

    • Author(s)
      高里 実
    • Organizer
      理研CDB-大塚製薬連携センター 第2回合同セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドとその応用利用への取り組みの現状2017

    • Author(s)
      高里 実
    • Organizer
      平成29年度 神戸再生医療勉強会(第5回)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイド作成系を利用したヒト腎臓発生機構の1細胞トランスクリプトーム解析2017

    • Author(s)
      高里 実
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞を用いた腎臓再創造の試み2017

    • Author(s)
      高里 実
    • Organizer
      奈良県立医科大学 平成29年度特別講演
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] REGULATING THE PATTERNING OF MESODERM AND GENERATING KIDNEY ORGANOIDS BY THE DIRECTED DIFFERENTIATION OF HUMAN PLURIPOTENT STEM CELLS2017

    • Author(s)
      高里 実
    • Organizer
      Stem Cells: The Next Generation, an ISSCR International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腎臓を創る2017

    • Author(s)
      高里 実
    • Organizer
      「細胞を創る」研究会 10.0
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulating mesoderm regionalization generates kidney organoids from human pluripotent stem cells2017

    • Author(s)
      高里 実
    • Organizer
      熊本大学HIGOプログラム最先端研究セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS 細胞由来腎臓オルガノイドと応用利用の可能性2017

    • Author(s)
      高里 実
    • Organizer
      iPS 細胞ビジネス協議会 第 25 回情報交換会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] MODELLING RENAL STRUCTURES IN HUMAN iPS CELLS-DERIVED KIDNEY ORGANOIDS2017

    • Author(s)
      高里 実
    • Organizer
      18th Congress of the European Society for Organ Transplantation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞由来腎臓オルガノイド応用利用の可能性2017

    • Author(s)
      高里 実
    • Organizer
      ベンチャー創設支援セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 腎臓オルガノイドと医療応用への道のり2017

    • Author(s)
      高里 実
    • Organizer
      発達腎研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来腎臓オルガノイド応用利用の可能性2017

    • Author(s)
      高里 実
    • Organizer
      神戸医療産業都市セミナー『神戸医療産業都市と理化学研究所のさらなる百年』
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 3次元腎臓組織をヒトiPS細胞から作る2017

    • Author(s)
      高里 実
    • Organizer
      日本組織培養学会第90回大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulating the mesoderm patterning generates kidney organoids from human pluripotent stem cells2017

    • Author(s)
      高里 実
    • Organizer
      第15回 幹細胞シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulating the patterning of the mesoderm during the directed differentiation of human PSCs2017

    • Author(s)
      高里 実
    • Organizer
      第50回 日本発生生物学会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2023-01-30  

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