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Elucidation of molecular basis of neuromuscular interactions in motor neuron diseases using disease specific iPSCs.

Research Project

Project/Area Number 18K15470
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionAichi Medical University

Principal Investigator

ITO Takuji  愛知医科大学, 加齢医科学研究所, 助教 (30794151)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords運動ニューロン / 骨格筋 / iPS細胞 / 運動ニューロン疾患 / タイムラプスイメージング / 神経筋接合部 / トランスクリプトーム / オプトジェネティクス / 球脊髄性筋萎縮症(SBMA) / 神経筋接合部(NMJ) / ゲノム編集 / 球脊髄性筋萎縮症(SBMA) / 神経筋接合部(NMJ)
Outline of Final Research Achievements

We developed a system to elucidate neuromuscular pathology using motor neuron disease-specific iPS cells. (1) We created a reporter to visualize the neuromuscular junction (NMJ) and succeeded in visualizing and quantifying NMJ formation. (2) We succeeded in capturing part of the phenotype using disease-specific iPS cells of SBMA.

Academic Significance and Societal Importance of the Research Achievements

疾患特異的iPS細胞を用いることで、患者由来運動ニューロンや骨格筋を用いた解析が可能になる。また、本解析で進める解析法は、様々な運動ニューロン疾患や筋疾患における神経・筋病態の解明に応用可能であり、神経・筋疾患における新たな病態解明と治療開発へと発展するものである。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (21 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] The SYNGAP1 3'UTR variant in ALS patients causes aberrant SYNGAP1 splicing and dendritic spine loss by recruiting HNRNPK2022

    • Author(s)
      Yokoi S, Ito T, Sahashi K, Nakatochi M, Tohnai G, Nakamura R, Fujioka Y, Ishigaki S, Udagawa T, Izumi Y, Morita M, Kano O, Oda M, Sone T, Okano H, Atsuta N, Katsuno M, Okada Y*, Sobue G*
    • Journal Title

      Journal of Neuroscience

      Volume: 42 Issue: 47 Pages: 8881-8896

    • DOI

      10.1523/jneurosci.0455-22.2022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Human Neuromuscular Tissue-on-a-Chip Model on a 24-Well-Plate-Format Compartmentalized Microfluidic Device2021

    • Author(s)
      Yamamoto K, Yamaoka N, Imaizumi Y, Nagashima T, Furutani T, Ito T, Okada Y, Honda H, Shimizu K
    • Journal Title

      Lab on a Chip

      Volume: 21 Issue: 10 Pages: 1897-1907

    • DOI

      10.1039/d1lc00048a

    • NAID

      120007169522

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simple and efficient differentiation of human iPSCs into contractible skeletal muscles for muscular disease modeling2021

    • Author(s)
      Rashid MI, Ito T, Shimojo D, Arimoto K, Onodera K, Okada R, Nagashima T, Yamamoto K, Khatun Z, Okano H, Sakurai H, Shimizu K, Doyu M, Okada Y
    • Journal Title

      bioRxiv

      Volume: 11.22.468571

    • Related Report
      2021 Research-status Report
    • Open Access
  • [Journal Article] PlexinA1 deficiency in BALB/cAJ mice leads to excessive self-grooming and reduced prepulse inhibition2020

    • Author(s)
      Mst Sharifa Jahan, Takuji Ito, Sachika Ichihashi, Takanobu Masuda, Md Eliusur Rahman Bhuiyan, Ikuko Takahashi, Hyota Takamatsu, Atsushi Kumanogoh, Takamasa Tsuzuki, Takayuki Negishi, Kazunori Yukawa
    • Journal Title

      IBRO Reports

      Volume: 22 Pages: 276-289

    • DOI

      10.1016/j.ibror.2020.10.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unveiling synapse pathology in spinal bulbar muscular atrophy by genome-wide transcriptome analysis of purified motor neurons derived from disease specific iPSCs2020

    • Author(s)
      Onodera K, Shimojo D, Ishihara Y, Yano M, Miya F, Banno H, Kuzumaki N, Ito T, Okada R, Ohyama M, Yoshida M, Tsunoda T, Katsuno M, Doyu M, Sobue G, Okano H, Okada Y
    • Journal Title

      Mol. Brain

      Volume: 13 Issue: 1 Pages: 18-18

    • DOI

      10.1186/s13041-020-0561-1

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of oxygen tension, acidosis, and cell density is crucial for neural differentiation of human induced pluripotent stem cells.2020

    • Author(s)
      Okada R, Onodera K, Ito T, Doyu M, Okano HJ, Okada Y
    • Journal Title

      Neurosci. Res.

      Volume: - Pages: 30043-2

    • DOI

      10.1016/j.neures.2020.01.015

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tandem paired nicking promotes precise genome editing with scarce interference by p532019

    • Author(s)
      Hyodo T, Rahman ML, Karnan S, Ito T, Toyoda A, Ota A, Wahiduzzaman M, Tsuzuki S, Okada Y, Hosokawa Y, Konishi H.
    • Journal Title

      Cell Rep.

      Volume: 30 Issue: 4 Pages: 1195-1207

    • DOI

      10.1016/j.celrep.2019.12.064

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Open-Chamber Co-Culture Microdevices for Single-Cell Analysis of Skeletal Muscle Myotubes and Motor Neurons with Neuromuscular Junctions2019

    • Author(s)
      Nao Yamaoka、Shimizu Kazunori、Yu Imaizumi、Takuji Ito、Yohei Okada、Hiroyuki Honda
    • Journal Title

      BioChip Journal

      Volume: in press Issue: 2 Pages: 127-132

    • DOI

      10.1007/s13206-018-3202-3

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] PlexinA1 is crucial for the midline crossing of callosal axons during corpus callosum development in BALB/cAJ mice2019

    • Author(s)
      Hossain Md. Mosharaf、Tsuzuki Takamasa、Sakakibara Kazuki、Imaizumi Fumitaka、Ikegaya Akihiro、Inagaki Mami、Takahashi Ikuko、Ito Takuji、Takamatsu Hyota、Kumanogoh Atsushi、Negishi Takayuki、Yukawa Kazunori
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 8 Pages: e0221440-e0221440

    • DOI

      10.1371/journal.pone.0221440

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Elucidating early pathophysiology of spinal-bulbar muscular atrophy using disease-specific iPSCs2022

    • Author(s)
      小野寺一成, 下門大祐, Bruno De Araujo Herculano1, 石原康晴, 依田真由子, 太田明伸, 矢野真人, 宮冬樹, Rashid Muhammad Irfanur, 伊藤卓治, 岡田梨奈, 角田達彦, 細川好孝, 道勇学, 祖父江元, 勝野雅央,岡野栄之,岡田洋平
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 疾患iPS細胞由来神経・筋共培養モデルを用いた運動ニューロン疾患の非細胞自律的神経変性を担う分子病態の解明2022

    • Author(s)
      伊藤卓治、ラシッド ムハンマド イルファヌール、小野寺一成、岡田梨奈、下門大祐、田中智史、勝野雅央、祖父江元、道勇学、岡野栄之、岡田洋平
    • Organizer
      第33回日本末梢神経学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Establishment of a more efficient disease model for ALS using feeder-free disease specific iPSCs2022

    • Author(s)
      Khatun Z, Onodera K, Yamaguchi S, Okada R, Ito T, Rashid MI, Inoue H, Aoki M, Okano H, Doyu M, Okada Y
    • Organizer
      第33回日本末梢神経学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 疾患iPS細胞由来神経・筋共培養モデルを用いた運動ニューロン疾患の非細胞自律的神経変性を担う分子病態の解明2022

    • Author(s)
      伊藤卓治、ラシッド ムハンマド イルファヌール、小野寺一成、岡田梨奈、下門大祐、田中智史、勝野雅央、祖父江元、道勇学、岡野栄之、岡田洋平
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Establishment of a more efficient disease model for ALS using feeder-free disease specific iPSCs2022

    • Author(s)
      Khatun Z, Onodera K, Yamaguchi S, Okada R, Ito T, Rashid MI, Inoue H, Aoki M, Okano H, Doyu M, Okada Y
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Bulk differentiation of iPSCs into contractible muscles for muscular disease modeling2022

    • Author(s)
      Rashid MI, Ito T, Miya F, Shimojo D, Arimoto K, Onodera K, Okada R, Nagashima T, Yamamoto K, Khatun Z, Okano H, Sakurai H, Shimizu K, Doyu M, Okada Y
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 疾患iPS細胞由来神経・筋共培養モデルを用いた運動ニューロン疾患の非細胞自律的神経変性を担う分子病態の解明2022

    • Author(s)
      伊藤卓治、ラシッド ムハンマド イルファヌール、小野寺一成、岡田梨奈、下門大祐、田中智史、勝野雅央、祖父江元、道勇学、岡野栄之、岡田洋平
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Establishment of a more efficient disease model for ALS using feeder-free disease specific iPSCs2022

    • Author(s)
      Khatun Z, Onodera K, Yamaguchi S, Okada R, Ito T, Rashid MI, Inoue H, Aoki M, Okano H, Doyu M, Okada Y
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 疾患特異的iPS細胞を用いた球脊髄性筋萎縮症(SBMA)の早期病態解明と治療開発2022

    • Author(s)
      小野寺一成、下門大祐、石原康晴、太田明伸、Muhammad Irfanur Rashid、伊藤卓治、岡田梨奈、細川好孝、道勇学、祖父江元、勝野雅央、岡野栄之、岡田洋平
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒトiPS細胞由来運動ニューロンと骨格筋を用いた機能的神経筋共培養モデルの構築2021

    • Author(s)
      伊藤 卓治, ラシッド ムハンマド, イルファヌール, 田中 智史, 下門 大祐, 岡野 栄之, 道勇 学, 岡田, 洋平
    • Organizer
      第44回日本神経科学?会 / CJK第1回国際会議(神戸)
    • Related Report
      2021 Research-status Report
  • [Presentation] ESTABLISHMENT OF IPSC-DERIVED NEUROMUSCULAR CO-CULTURE MODEL FOR THE ANALYSIS OF NON-CELL AUTONOMOUS NEURODEGENERATION IN MOTOR NEURON DISEASES2021

    • Author(s)
      Takuji Ito, Muhammad Irfanur Rashid, Satoshi Tanaka, Daisuke Shimojo, Hideyuki Okano, Manabu Doyu, Yohei Okada
    • Organizer
      ISSCR/JSRM 2021 Tokyo International Symposium (Tokyo)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 疾患iPS細胞による神経・筋共培養を活用した神経変性疾患の病態解析2020

    • Author(s)
      伊藤卓治, 小野寺一成, 小野寺一成, 下門大祐, 下門大祐, 田中智史, 田中智史, 岡田梨奈, RASHID Muhammad Irfanur, 道勇学, 岡野栄之, 岡田洋平
    • Organizer
      日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] ELUCIDATION OF NONCELL AUTONOMOUS NEURODEGENERATION IN SPINAL AND BULBAR MUSCULAR ATROPHY USING IPSC-DERIVED NEUROMUSCULAR MODELS2019

    • Author(s)
      Ito T, Tanaka S, Shimojo D, Doyu M, Okano H, Okada Y
    • Organizer
      International Society for Stem Cell Research(ISSCR)2019 Annual Meeting(Los Angeles)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 疾患特異的iPS細胞を用いた神経変性疾患の早期病態の解明2019

    • Author(s)
      岡田洋平、小野寺一成、依田真由子、伊藤卓治、岡田梨奈、勝野雅央、道勇学、祖父江元、岡野栄之
    • Organizer
      新学術領域「脳たんぱく質老化と認知症制御」第9回班員会議
    • Related Report
      2018 Research-status Report
  • [Presentation] 疾患iPS細胞による神経・筋共培養を活用した新たな病態解析システムの構築2019

    • Author(s)
      伊藤卓治、田中智史、下門大祐、道勇学、岡野栄之、岡田洋平
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] マイクロデバイスを用いたヒトiPS由来運動神経細胞と骨格筋細胞の三次元共培養2019

    • Author(s)
      山岡奈央、清水一憲、今泉裕、伊藤卓治、岡田洋平、本多裕之
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pathophysiological analysis of spinal and bulbar muscular atrophy using disease-specific iPSCs2018

    • Author(s)
      Onoderea K, Ito T, Shimojo D, Ishihara Y, Doyu M, Katsuno M, Okano H, Sobue G, Okada Y.
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pathophysiological analysis of Spinal-bulbar muscular atrophy using disease specific iPSCs.2018

    • Author(s)
      Okada Y, Onodera K, Ito T, Shimojo D, Okada R, Ishihara Y,Tanaka S, Katsuno M,Doyu M, Sobue G,Okano H.
    • Organizer
      ISSCR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of iPSC-derived neuromuscular models for the analysis of non-cell autonomousneurodegeneration in motor neuron diseases.2018

    • Author(s)
      Ito T, Tanaka S, Shimojo D, Doyu M, Okano H, Okada Y.
    • Organizer
      ISSCR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 疾患特異的iPS細胞を用いた神経変性疾患の早期病態の解明2018

    • Author(s)
      岡田洋平、小野寺一成、依田真由子、伊藤卓治、勝野雅央、道勇学、祖父江元、岡野栄之
    • Organizer
      新学術領域「脳たんぱく質老化と認知症制御」第8回班員会議・第4回リトリート
    • Related Report
      2018 Research-status Report
  • [Presentation] iPS細胞を用いた神経筋接合部可視化システムおよび機能評価系の構築2018

    • Author(s)
      伊藤卓治、田中智史、下門大祐、道勇学、岡野栄之、岡田洋平
    • Organizer
      新学術領域「脳たんぱく質老化と認知症制御」第8回班員会議・第4回リトリート
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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