An analysis of cerebellar histogenesis generated from human pluripotent stem cells

• Project/Area Number: 15K07089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Muguruma Keiko 国立研究開発法人理化学研究所, 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): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 小脳 / ヒト多能性幹細胞 / プルキンエ細胞 / 神経分化 / 三次元立体培養 / 自己組織化 / 脳オルガノイド / 三次元培養 / 神経変性

Outline of Final Research Achievements

The R&D PI was engaged in the pioneering works on the development of the self-organizing culture of pluripotent stem cells (PSCs) for brain tissue formation (brain organoid). Using this technique, she developed efficient methods for differentiation of PSCs into cerebellar neurons and cerebellar tissues. In this R&D project, she succeeded in construction of human disease models for cerebellar ataxia by differentiation of the patient-derived iPSCs.

Research Products

• [Journal Article] Self-organizing cortex generated from human iPSCs with combination of FGF2 and ambient oxygen. (2018)
  • Author(s): Eguchi N, Sora I, Muguruma K.
  • Journal Title: Biochem Biophys Res Commun Volume: 498 Issue: 4 Pages: 729-735
  • DOI: 10.1016/j.bbrc.2018.03.049
  • NAID: 120006462318
  • Peer Reviewed / Open Access
• [Journal Article] Self-organized cerebellar tissue from human pluripotent stem cells and disease modeling with patient-derived iPSCs (2018)
  • Author(s): Muguruma K
  • Journal Title: Cerebellum Volume: 17 Issue: 1 Pages: 37-41
  • DOI: 10.1007/s12311-017-0905-2
  • Peer Reviewed / Open Access
• [Journal Article] 3D culture for self-formation of the cerebellum from human pluripotent stem cells through induction of the isthmic organizer (2017)
  • Author(s): Muguruma K
  • Journal Title: Methods in Molecular Biology Volume: 1597 Pages: 31-41
  • DOI: 10.1007/978-1-4939-6949-4_3
  • ISBN: 9781493969470, 9781493969494
  • Open Access
• [Journal Article] Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs. (2016)
  • Author(s): Ishida Y, Kawakami H, Kitajima H, Nishiyama A, Sasai Y, Inoue H, Muguruma K.
  • Journal Title: Cell Rep Volume: 17 Issue: 6 Pages: 1482-1490
  • DOI: 10.1016/j.celrep.2016.10.026
  • NAID: 120006223645
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] iPS細胞から立体脳組織への分化誘導と疾患研究 (2016)
  • Author(s): 六車 恵子
  • Journal Title: 実験医学 Volume: 34 Pages: 551-556
• [Journal Article] A mutation in the low voltage -gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. (2015)
  • Author(s): Morino H., Matsuda Y., Muguruma K., Miyamoto R., Ohsawa R., Ohtake T., Otobe R., Watanabe M., Maruyama H., Hashimoto K., Kawakami H.
  • Journal Title: Molecular Brain Volume: 8 Issue: 1 Pages: 1-9
  • DOI: 10.1186/s13041-015-0180-4
  • Peer Reviewed / Open Access
• [Presentation] Construction of iPSC-derived functional brain tissue for investigation of disease mechanisms (2018)
  • Author(s): Keiko Muguruma
  • Organizer: 2018 Keystone Symposia in iPSCs
  • Int'l Joint Research / Invited
• [Presentation] Investigation of ontogenesis and pathogenesis with self-organized brain structure from human iPS cells (2018)
  • Author(s): Keiko Muguruma
  • Organizer: The 18th World Congress of Basic and Clinical Pharmacology
  • Int'l Joint Research / Invited
• [Presentation] Investigation of neurodegenerative disease utilizing patient-specific iPS cells. (2017)
  • Author(s): Keiko Muguruma
  • Organizer: SELECT BIO Advances in Drug Discovery 2017
  • Place of Presentation: Genome Campus Conference Centre (Cambridge, UK)
  • Year and Date: 2017-03-07
  • Int'l Joint Research / Invited
• [Presentation] 疾患iPS細胞由来の3次元立体大脳組織を活用したてんかん研究の展望 (2017)
  • Author(s): 六車恵子
  • Organizer: 第51回日本てんかん学会学術集会
  • Invited
• [Presentation] Disease modeling with patient derived iPS cells. (2017)
  • Author(s): Keiko Muguruma
  • Organizer: SRC 2017 8th International Symposium
  • Int'l Joint Research / Invited
• [Presentation] 患者由来iPS細胞を活用した神経変性疾患研究 (2016)
  • Author(s): 六車恵子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] 試験管内で小脳を作る：iPS細胞を活用した疾患研究 (2016)
  • Author(s): 六車恵子
  • Organizer: 第10回パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 京都ホテルオークラ（京都府京都市）
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] Disease modeling with patient derived iPSCs. (2016)
  • Author(s): Keiko Muguruma
  • Organizer: Cell Symposia 10 Years of iPSCs
  • Place of Presentation: Claremont Hotel & Spa (Barkeley, CA, USA)
  • Year and Date: 2016-09-27
  • Int'l Joint Research
• [Presentation] ヒトES/iPS細胞の自己組織課による小脳形成 (2016)
  • Author(s): 六車恵子
  • Organizer: 岐阜大・岐阜薬大連携 第13回岐阜神経研究会
  • Place of Presentation: 岐阜大学医学部（岐阜県岐阜市）
  • Year and Date: 2016-06-15
  • Invited
• [Presentation] 患者由来iPS細胞を活用した脊髄小脳変性症の疾患モデル開発 (2016)
  • Author(s): 六車恵子
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2016-05-20
  • Invited
• [Presentation] 多能性幹細胞の小脳細胞分化と疾患モデリング (2016)
  • Author(s): 六車 恵子
  • Organizer: 第15回日本再生医療学会総会 シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-19
  • Invited
• [Presentation] 小脳を作る (2016)
  • Author(s): 六車 恵子
  • Organizer: 第6回小脳研究会 学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2016-01-08
  • Invited
• [Presentation] iPS細胞を用いた大脳・小脳希少難治性疾患研究への取り組み (2015)
  • Author(s): 六車 恵子
  • Organizer: 日本動物実験代替法学会第28回大会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2015-12-12
  • Invited
• [Presentation] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. (2015)
  • Author(s): Muguruma K., Kawakami H., Hashimoto K., Sasai Y.
  • Organizer: Society for Neuroscience Annual Meeting 2015
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. (2015)
  • Author(s): Muguruma K., Nishiyama A., Kawakami H., Hashimoto K., Sasai Y.
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-07-28
  • Int'l Joint Research
• [Presentation] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. (2015)
  • Author(s): Muguruma K
  • Organizer: ISSCR 13th Annual Meeting
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2015-06-25
  • Int'l Joint Research
• [Presentation] Generation of cerebellar Purkinje cells from human pluripotent stem cells. (2015)
  • Author(s): Muguruma K
  • Organizer: Gordon Research Conference CAG triplet Repeat 2015
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2015-05-31
  • Int'l Joint Research
• [Book] Organ Regeneration (2017)
  • Author(s): Muguruma K (Ed. Tsuji T.)
  • Total Pages: 248
  • Publisher: Humana Press
  • ISBN: 9781493969494
• [Book] 運動失調のみかた、考えかた (2017)
  • Author(s): 六車恵子（宇川義一 編）
  • Total Pages: 358
  • Publisher: 中外医学社
  • ISBN: 9784498228900
• [Book] Annual Review神経2017 (2017)
  • Author(s): 六車恵子
  • Total Pages: 281
  • Publisher: 中外医学社
  • ISBN: 9784498228764
• [Book] Clinical Neuroscience（臨床神経科学） (2017)
  • Author(s): 六車恵子
  • Publisher: 中外医学社
• [Book] Annual Review 神経2017 (2017)
  • Author(s): 六車恵子
  • Total Pages: 279
  • Publisher: 中外医学社