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Self-organization of cerebellar tissue in 3D culture of human pluripotent stem cells

Research Project

Project/Area Number 24570242
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

MUGURUMA Keiko  独立行政法人理化学研究所, 多細胞システム形成研究センター, 専門職研究員 (30209978)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords小脳 / ヒト多能性幹細胞 / 神経分化 / 3次元培養 / 自己組織化 / 三次元培養
Outline of Final Research Achievements

Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that both Purkinje cells and granule cells could be effectively generated from human pluripotent stem (ES and iPS) cells by recapitulating the self-inducitive signaling microenvironments of the isthmic organizer. The cerebellar neuroepithelium (NE), formed in response to the combination of Fgf2 and insulin, differentiated into electrophysiologically functional Purkinje cells. The addition of Fgf19 and CXCL12 promotes the generation a continuous cerebellar plate NE and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human pluripotent stem cells-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.2015

    • Author(s)
      Muguruma K, et al.
    • Journal Title

      Cell Reports

      Volume: 10 Issue: 4 Pages: 537-550

    • DOI

      10.1016/j.celrep.2014.12.051

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ヒト多能性幹細胞の自己組織的分化による小脳組織の構築2015

    • Author(s)
      六車 恵子
    • Journal Title

      細胞工学

      Volume: 34(7)

    • Related Report
      2014 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Self-formation of optic cups and storable stratified neural retina from human ESCs.2012

    • Author(s)
      Nakano T
    • Journal Title

      Cell Stem Cell

      Volume: 10 Issue: 6 Pages: 771785-771785

    • DOI

      10.1016/j.stem.2012.05.009

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vitro recapitulation of neural deveopment using embryonic stem cells: From neurogenesis to histogenesis.2012

    • Author(s)
      Muguruma K
    • Journal Title

      Dev. Growth Differ

      Volume: 54(3) Pages: 349-357

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト多能性幹細胞の3次元培養による極性を伴った小脳組織の自己組織的な形成2015

    • Author(s)
      六車 恵子
    • Organizer
      日本神経科学
    • Place of Presentation
      神戸、兵庫県
    • Year and Date
      2015-07-28 – 2015-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.2015

    • Author(s)
      Muguruma K.
    • Organizer
      ISSCR
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24 – 2015-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Generation of cerebellar Purkinje cells from human pluripotent stem cells.2015

    • Author(s)
      Muguruma K.
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Renaissance Tuscany Il Ciocco Lucca (Barga), Italy
    • Year and Date
      2015-05-31 – 2015-06-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多能性幹細胞からの脳発生の再現

    • Author(s)
      六車 恵子
    • Organizer
      (独)国立精神・神経医療研究センター 神経研究所所内セミナー
    • Place of Presentation
      東京都小平市 神経研究所
    • Related Report
      2012 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 小脳前駆組織の製造方法2014

    • Inventor(s)
      笹井芳樹、六車恵子
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-182758
    • Filing Date
      2014-09-08
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトES細胞用培養容器2012

    • Inventor(s)
      笹井芳樹、六車恵子、塚田亮平、田中速雄
    • Industrial Property Rights Holder
      理化学研究所、住友ベークライト株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-131430
    • Filing Date
      2012-06-08
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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