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2019 Fiscal Year Annual Research Report

Elucidation of early pathology of motor neuron diseases using disease specific iPSCs

Research Project

Project/Area Number 19H03576
Research InstitutionAichi Medical University

Principal Investigator

岡田 洋平  愛知医科大学, 医学部, 准教授 (30383714)

Co-Investigator(Kenkyū-buntansha) 伊藤 卓治  愛知医科大学, 公私立大学の部局等, 客員研究員 (30794151)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywords疾患iPS細胞 / 運動ニューロン疾患 / 早期病態
Outline of Annual Research Achievements

SBMA疾患iPS細胞由来運動ニューロンを用いて同定した早期病態関連分子について、その関連分子も含めて、患者および健常者iPS細胞由来運動ニューロンにおける発現解析を行った。また、レンチウイルスを用いて、これらの分子を健常者iPS細胞由来運動ニューロンに強制発現し、病態再現を検討した。さらに、早期診断のためのバイオマーカーとなり得るかについて、患者検体を用いて検討した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初の予定通り進捗している。

Strategy for Future Research Activity

早期病態関連分子のノックダウンによる表現型のレスキューを検討し、これらの分子の病態への関与を検証する。また、これらの分子に関連する阻害剤等を用いて病態のレスキューを行い、SBMAの治療標的となり得るかを検討する。
また、運動ニューロンと骨格筋の相互作用に着目し、早期病態関連分子とその関連分子の骨格筋における発現を解析するとともに、これらの分子が骨格筋に及ぼす影響を検討する予定である。

  • Research Products

    (15 results)

All 2021 2020 2019 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Modulation of oxygen tension, acidosis, and cell density is crucial for neural differentiation of human induced pluripotent stem cells.2021

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

      Neurosci. Res.

      Volume: 153 Pages: 34-42

    • DOI

      10.1016/j.neures.2020.01.015.

    • Peer Reviewed
  • [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 Pages: 18

    • DOI

      10.1186/s13041-020-0561-1. doi: 10.1186/s13041-020-0561-1

    • 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)
      Yamaoka N, Shimizu K, Imaizumi Y, Ito T, Okada Y, Honda H.
    • Journal Title

      BioChip Journal

      Volume: 13 Pages: 127-132

    • DOI

      https://doi.org/10.1007/s13206-018-3202-3

    • Peer Reviewed
  • [Journal Article] Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons.2019

    • Author(s)
      Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J, Funayama R, Fujishima F, Mitsuzawa S, Ikeda K, Ono H, Shijo T, Osana S, Shirota M, Nakagawa T, Kitajima Y, Nishiyama A, Izumi R, Morimoto S, Okada Y, Kamei T, Nishida M, Nogami M, Kaneda S, Ikeuchi Y, Mitsuhashi H, Nakayama K, Fujii T, Warita H, Okano H
    • Journal Title

      EBioMedicine.

      Volume: 45 Pages: 362-378

    • DOI

      10.1016/j.ebiom.2019.06.013. Epub 2019 Jun 29.

    • Peer Reviewed / Open Access
  • [Journal Article] Src inhibition attenuates polyglutamine-mediated neuromuscular degeneration in spinal and bulbar muscular atrophy2019

    • Author(s)
      Iida M, Sahashi K, Kondo N, Nakatsuji H, Tohnai G, Tsutsumi Y, Noda S, Murakami A, Onodera K, Okada Y, Nakatochi M, Okabe Y, Shimizu S, Mizuno M, Adachi H, Okano H, Sobue G, Katsuno M
    • Journal Title

      Nat. Commun.

      Volume: 10 Pages: 4262

    • DOI

      10.1038/s41467-019-12282-12287.

    • Peer Reviewed / Open Access
  • [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 Pages: 1195-1207

    • DOI

      10.1016/j.celrep.2019.12.064.

    • Peer Reviewed / Open Access
  • [Journal Article] 疾患特異的iPS細胞を用いた神経変性疾患の病態解析と新規治療法開発2019

    • Author(s)
      岡田洋平
    • Journal Title

      臨床雑誌内科

      Volume: 123 Pages: 1315-1319

    • Peer Reviewed / Open Access
  • [Presentation] Pathophysiological analysis of spinal and bulbar muscular atrophy using disease-specific iPSCs.2019

    • Author(s)
      Onodera K, Shimojo D, Yoda M, Ishihara Y, Ito T, Okada R, Doyu M, Katsuno M, Okano H, Sobue G, Okada Y
    • Organizer
      第60回日本神経学会学術大会
  • [Presentation] FUS depletion induces spine abnormality and SynGAP depletion in hiPSC-derived motor neuron.2019

    • Author(s)
      Yokoi S, Ito T, Sahashi K, Ishigaki S, Katsuno M, Okada Y, Sobue G.
    • Organizer
      第60回日本神経学会学術大会
  • [Presentation] The effects of hypoxia on differentiation and maturation of human induced pluripotent stem cell-derived neural progenitors.2019

    • Author(s)
      Okada Y, Okada R, Li J, Onodera K, Ito T, Okano HJ, Doyu M
    • Organizer
      ISSCR 2019 Annual Meeting, LosAngeles
    • Int'l Joint Research
  • [Presentation] Reconstruction of motor function in peripheral nerves by transplanatation of human iPSC-derived motor neuron progenitors.2019

    • Author(s)
      Niwa S, Saeki M, Shinkai H, Kurimoto S, Hirata H, Doyu M, Okada Y
    • Organizer
      ISSCR 2019 Annual Meeting, LosAngeles
    • Int'l Joint Research
  • [Presentation] Elucidation of non-cell autonomous neurodegeneration in spinal and bulbar muscular atrophy using iPSC-derived neuromuscular models.2019

    • Author(s)
      Ito T, Tanaka S, Shimojo D, Doyu M, Okano H, Okada Y
    • Organizer
      ISSCR 2019 Annual Meeting, LosAngeles
    • Int'l Joint Research
  • [Presentation] iPS細胞を用いた神経疾患研究2019

    • Author(s)
      岡田洋平
    • Organizer
      SBMAの会 第8回医療セミナー
    • Invited
  • [Presentation] iPS細胞を用いたNMJ形成②2019

    • Author(s)
      岡田洋平
    • Organizer
      AMED再生医療実現拠点ネットワークプログラム「疾患特異的iPS細胞の利活用促進・難病研究加速プログラム」研究拠点I疾患別ミーティング
    • Invited
  • [Remarks] 愛知医科大学 神経内科

    • URL

      https://www.aichi-med-u.ac.jp/su06/su0607/su060703/02.html

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Published: 2021-01-27  

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