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Classification of sporadic Parkinson's disease from patient iPS cell phenotypes

Research Project

Project/Area Number 21H02814
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionJuntendo University

Principal Investigator

AKAMATSU WADO  順天堂大学, 大学院医学研究科, 教授 (60338184)

Co-Investigator(Kenkyū-buntansha) 清田 純  国立研究開発法人理化学研究所, 情報統合本部, チームリーダー (40793790)
太田 禎生  東京大学, 先端科学技術研究センター, 准教授 (70731214)
石川 景一  順天堂大学, 大学院医学研究科, 准教授 (90733973)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2022: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsパーキンソン病 / iPS細胞 / 層別化 / 神経分化 / 機械学習 / 深層学習 / 高速イメージャー / 高速3Dフローイメージャー
Outline of Research at the Start

本研究は申請者が現在も整備を進めている遺伝性・孤発性PD-iPS細胞ライブラリの表現型解析において、孤発性PDの画像データの機械学習を用いた直接解析および高速フローイメージャーを用いた細胞情報解析と画像化を用いることによって客観性とスループットを向上させ、孤発性PD症例の細胞病態表現型に基づく分類を可能にすることを目的とする。その結果として、現在は画一的なPDの治療が各症例の細胞表現型から分類した最適な治療法への確立に繋がることが期待できる。

Outline of Final Research Achievements

We considered that the stratification of sporadic cases, which account for 90% of Parkinson's disease cases, would lead to the development of optimal treatment. The aim of this study was to construct an original system that could objectively classify each case of iPS cell-derived neurons from hundreds of patients with sporadic Parkinson's disease , which had been established by the principal investigator. (1) Developing an algorithm to extract only cell bodies, which is the area of interest (2) By increasing the number of samples and types of hereditary cases, we succeeded in increasing the correct response rate to 100% for hereditary cases that show mitophagy abnormalities. Furthermore, the morphology of cells was distinguished using an AI-based high-speed imager, and a high discrimination system of 74-79% was achieved for disease groups in undifferentiated iPS cells.

Academic Significance and Societal Importance of the Research Achievements

本研究は、多様性のある孤発性PDのうち特定の細胞表現型もしくは細胞における薬剤反応性から特定の集団を抽出し、患者からのデータ取得が比較的に容易な遺伝情報や臨床情報を教師データとして深層学習を活用することによって孤発性PD症例の細胞病態表現型の差異を層別化する因子を同定することを目的とするが、その結果として、患者検体から比較的簡便に解析可能な層別化バイオマーカーが同定され、現在は画一的なPDの治療が各症例の層別化から選択した最適な治療法への確立に繋がることが期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (11 results)

All 2024 2023

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 11 results)

  • [Journal Article] Generation of one induced pluripotent stem cell line JUCGRMi004-A from a Charcot-Marie-Tooth disease type 1A (CMT1A) patient with PMP22 duplication2024

    • Author(s)
      Liu Xing、Ishikawa Kei-ichi、Hattori Nobutaka、Akamatsu Wado
    • Journal Title

      Stem Cell Research

      Volume: 77 Pages: 103401-103401

    • DOI

      10.1016/j.scr.2024.103401

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of hiPSCs (JUCGRMi003-A) from a patient with Parkinson’s disease with PARK2 mutation2024

    • Author(s)
      Ishikawa Kei-ichi、Okuzumi Ayami、Yoshino Hiroyo、Hattori Nobutaka、Akamatsu Wado
    • Journal Title

      Stem Cell Research

      Volume: 76 Pages: 103323-103323

    • DOI

      10.1016/j.scr.2024.103323

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of three clones (JUCGRMi002-A, B, C) of induced pluripotent stem cells from a Parkinson’s disease patient with SNCA duplication2024

    • Author(s)
      Ishikawa Kei-ichi、Shiga Takahiro、Yoshino Hiroyo、Nishioka Kenya、Hattori Nobutaka、Akamatsu Wado
    • Journal Title

      Stem Cell Research

      Volume: 74 Pages: 103296-103296

    • DOI

      10.1016/j.scr.2023.103296

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a control iPS cell line (JUCGRMi005-A) with no abnormalities in Parkinson's disease-related genes2024

    • Author(s)
      Ishikawa Kei-ichi、Shiga Takahiro、Funayama Manabu、Hattori Nobutaka、Akamatsu Wado
    • Journal Title

      Stem Cell Research

      Volume: 74 Pages: 103271-103271

    • DOI

      10.1016/j.scr.2023.103271

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a control iPS cell line (JUCGRMi006-A) with no abnormalities in Parkinson's disease-related genes2024

    • Author(s)
      Ishikawa Kei-ichi、Shiga Takahiro、Funayama Manabu、Hattori Nobutaka、Akamatsu Wado
    • Journal Title

      Stem Cell Research

      Volume: 74 Pages: 103270-103270

    • DOI

      10.1016/j.scr.2023.103270

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC)2023

    • Author(s)
      Liu Lu、Yang Jiahao、Otani Yoshinori、Shiga Takahiro、Yamaguchi Akihiro、Oda Yasuaki、Hattori Miho、Goto Tsukimi、Ishibashi Shuichi、Kawashima-Sonoyama Yuki、Ishihara Takaya、Matsuzaki Yumi、Akamatsu Wado、Fujitani Masashi、Taketani Takeshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 24 Pages: 17186-17186

    • DOI

      10.3390/ijms242417186

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-read sequencing resolves a complex structural variant in PRKN Parkinson’s disease2023

    • Author(s)
      Daida K, Funayama M, Billingsley KJ, Malik L, Miano-Burkhardt A, Leonard HL, Makarious MB, Iwaki H, Ding J, Gibbs JR, Ishiguro M, Yoshino H, Ogaki K, Oyama G, Nishioka K, Nonaka R, Akamatsu W, Blauwendraat C, Hattori N
    • Journal Title

      Movement Disorders

      Volume: 38 Issue: 12 Pages: 2249-2257

    • DOI

      10.1002/mds.29610

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced ER-mitochondrial contact sites and mitochondrial Ca2+ flux in PRKN-mutant patient tyrosine hydroxylase reporter iPSC lines.2023

    • Author(s)
      Yokota M, Yoshino Y, Hosoi M, Hashimoto R, Kakuta S, Shiga T, Ishikawa KI, Okano H, Hattori N, Akamatsu W, Koike M.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 11

    • DOI

      10.3389/fcell.2023.1171440

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of casein kinase 1 epsilon/delta (Csnk1e/d) in the pathogenesis of familial Parkinson's disease caused by <scp>CHCHD2</scp>2023

    • Author(s)
      Torii Satoru、Arakawa Satoko、Sato Shigeto、Ishikawa Kei‐ichi、Taniguchi Daisuke、Sakurai Hajime Tajima、Honda Shinya、Hiraoka Yuuichi、Ono Masaya、Akamatsu Wado、Hattori Nobutaka、Shimizu Shigeomi
    • Journal Title

      EMBO Molecular Medicine

      Volume: 15 Issue: 9

    • DOI

      10.15252/emmm.202317451

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A defined method for differentiating human iPSCs into midbrain dopaminergic progenitors that safely restore motor deficits in Parkinson’s disease2023

    • Author(s)
      Nakamura Ryota、Nonaka Risa、Oyama Genko、Jo Takayuki、Kamo Hikaru、Nuermaimaiti Maierdanjiang、Akamatsu Wado、Ishikawa Kei-ichi、Hattori Nobutaka
    • Journal Title

      Frontiers in Neuroscience

      Volume: 17

    • DOI

      10.3389/fnins.2023.1202027

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and characterization of a human iPSC line (JUFMDOi007-A) from a patient with Usher syndrome due to mutation in USH2A2023

    • Author(s)
      Ukaji Takao、Takahashi-Shibata Mikako、Arai Daisuke、Tsutsumi Harumi、Tajima Shori、Akamatsu Wado、Matsumoto Fumihiko、Ikeda Katsuhisa、Usami Shin-ichi、Kamiya Kazusaku
    • Journal Title

      Stem Cell Research

      Volume: 69 Pages: 103100-103100

    • DOI

      10.1016/j.scr.2023.103100

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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