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Identification of genomic changes and their therapeutic effects in neuronally-differentiated induced pluripotent stem cells of autistic patients

Research Project

Project/Area Number 25670473
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionUniversity of Yamanashi

Principal Investigator

KUBOTA Takeo  山梨大学, 総合研究部, 教授 (70293511)

Co-Investigator(Kenkyū-buntansha) TOYODA Atsushi  国立遺伝学研究所, 生物遺伝資源情報総合センター, 特任准教授 (10267495)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエピジェネティクス / エピゲノム / 治療薬 / iPS細胞 / レット症候群 / 自閉症 / 遺伝子発現制御 / バルプロ酸ナトリウム / 遺伝子発現 / てんかん
Outline of Final Research Achievements

We investigated abnormalities in the neuronal cells differentiated from the induced pluripotent stem cells (iPSC) derived from Rett syndrome patients, a representative autistic disorder caused by MECP2 mutations. As a result, we found abnormal expression of astrocyte-specific genes. Furthermore, we found that the chemicals, target to HDAC and Sin3 which are parts of MeCP2 protein complex, up-regulated Rett syndrome- and autism-associated genes. These findings suggest that malfunction of MeCP2-induced genomic changes may underlie the alteration of astrocyte-specific genes, and indicate that the chamicals examined possibly recover the gene expression which were down-regulated in Rett and autistic patients.

Report

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

    (26 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Invited: 16 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Understanding the epigenetics of neurodevelopmental disorders and DOHaD.2015

    • Author(s)
      Kubota T, Miyake K, Hariya N, Mochizuki K.
    • Journal Title

      J Dev Orig Health Dis

      Volume: 24 Issue: 2 Pages: 1-9

    • DOI

      10.1017/s2040174415000057

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage.2015

    • Author(s)
      Andoh-Noda T, Akamatsu W, Miyake K, MatsumotoT, Yamaguchi R, Sanosaka T, Okada Y, Kobayashi T, Ohyama M, Nakashima K, Kurosawa H, Kubota T, Okano H.
    • Journal Title

      Mol Brain

      Volume: 未定

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epigenetics as a basis for diagnosis of neurodevelopmental disorders: challenges and opportunities.2014

    • Author(s)
      Kubota T, Miyake K, Hariya M, Mochizuki K.
    • Journal Title

      Expert Rev Mol Diagn

      Volume: 14 Issue: 6 Pages: 685-697

    • DOI

      10.1586/14737159.2014.925805

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of genomic and epigenomic expression in monozygotic twins discordant for Rett syndrome2013

    • Author(s)
      Miyake K, Yang C, Minakuchi Y, Ohori K, Soutome M, Hirasawa T, Kazuki Y, Adachi N, Suzuki S, Itoh M, Goto Y, Andoh T, Kurosawa H, Akamatsu W, Oyama M, Okano H, Oshimura M, Sasaki M, Toyoda A, Kubota T
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 6 Pages: e66729-e66729

    • DOI

      10.1371/journal.pone.0066729

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of epigenetics in Rett sydro me2013

    • Author(s)
      Kubota T, Miyake K, Hirasawa T
    • Journal Title

      Epigenomics

      Volume: 5 Issue: 5 Pages: 583-592

    • DOI

      10.2217/epi.13.54

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetics in neurodevelopmental and mental disorders2013

    • Author(s)
      Kubota T, Miyake K, Hirasawa T
    • Journal Title

      Med Epigenet

      Volume: 1 Pages: 61-67

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 特別講演I「エピジェネティクスに基づく健康戦略」2014

    • Author(s)
      久保田健夫
    • Organizer
      第5回 岐阜薬科大学機能性健康食品(蜂産品)研究講演会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜県岐阜市)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Epigenomics in Chronic Diseases. シンポジウム2S17 At the Molecular Crossroad of Metabolism and Epigenetics(代謝とエピジェネティクスの分子交差点).2014

    • Author(s)
      久保田健夫
    • Organizer
      第37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
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 臨床エピジェネティクス研究~今、どこにむかっているのか~.2014

    • Author(s)
      久保田健夫
    • Organizer
      千葉県がんセンター研究所集談会
    • Place of Presentation
      千葉県がんセンター(千葉県千葉市)
    • Year and Date
      2014-11-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 発達障害とエピジェネティクス. シンポジウム エピジェネティクス研究が拓くストレス科学の世界.2014

    • Author(s)
      三宅邦夫、久保田健夫
    • Organizer
      第30回日本ストレス学会
    • Place of Presentation
      日本大学文理学部百周年記念館(東京都世田谷区)
    • Year and Date
      2014-11-07 – 2014-11-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Clinical application of an anion exchange HPLC column that distinguishes DNA methylation status.2014

    • Author(s)
      Miyake K, Yamada Y, Yotani T, Kubota. T.
    • Organizer
      The American society of Human Genetics 64nd Annual Meeting
    • Place of Presentation
      サンディエゴ市(米国)
    • Year and Date
      2014-10-18 – 2014-10-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Epigenetics as a basis for diagnosis and treatment of Neurodevelopmental Disorders.2014

    • Author(s)
      Kubota T.
    • Organizer
      Epigenomics & Metabolomics Symposia-2014
    • Place of Presentation
      ボストン市(米国)
    • Year and Date
      2014-08-25 – 2014-08-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 自閉症疾患(Rett症候群)の病態解明とその問題点. シンポジウム1 iPS細胞を用いた小児神経疾患の病態解明とその問題点.2014

    • Author(s)
      久保田健夫
    • Organizer
      第56回日本小児神経学会総会
    • Place of Presentation
      アクトシティー浜松(静岡県浜松市)
    • Year and Date
      2014-05-28 – 2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 発達障害にかかわる要因について:オーバービュー. シンポジウム4 発達障害はいつ形成されるか?先天性?後天性?あるは両方か?~発症および病態修飾メカニズムについて~.2014

    • Author(s)
      久保田健夫
    • Organizer
      6回日本小児神経学会総会
    • Place of Presentation
      アクトシティー浜松(静岡県浜松市)
    • Year and Date
      2014-05-28 – 2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] エピゲノム~環境を反映するゲノム情報~. シンポジウム1「栄養とエピゲノム」.2013

    • Author(s)
      久保田健夫
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋大学(愛知県名古屋市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 自閉症のエピジェネティックな理解 シンポジウム1「自閉症の神経科学的研究」2013

    • Author(s)
      久保田健夫
    • Organizer
      第55回日本小児神経学会総会
    • Place of Presentation
      iichiko総合文化センター(大分県大分市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Epigenetics in Neurodevelopmental Disorders2013

    • Author(s)
      Kubota T
    • Organizer
      Epigenomics & Metabolomics Symposia-2013
    • Place of Presentation
      ハーバード大学(ボストン、米国)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 胎生期環境と疾患素因としてのエピゲノム変化. シンポジウム8「ARTとエピゲノム-児の将来を見据えて-」2013

    • Author(s)
      久保田健夫、小幡千枝、前山弘毅、平澤孝枝
    • Organizer
      第31回日本受精着床学会総会・学術講演会
    • Place of Presentation
      別府国際コンベンションセンター(大分県別府市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 精神発達とエピジェネティクス. 精神疾患のジェネティクスとエピジェネティクス.2013

    • Author(s)
      久保田健夫
    • Organizer
      日本心理学会第77回大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 妊婦の低栄養と胎児のエピジェネティクス変化. ワークショップ5「若年女性の栄養管理を考える –DOHaDを見据えた栄養管理」.2013

    • Author(s)
      久保田健夫、平澤孝枝
    • Organizer
      第35回日本臨床栄養学会総会・第34回日本臨床栄養協会総会(第11回大連合大会)
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Environment, Epigenetics and Neurodevelopment. Pre-Congress Workshop 2: Epigenetic Analysis/ EWAS.2013

    • Author(s)
      Kubota T
    • Organizer
      Pre-Congress Workshop 2: Epigenetic Analysis/ EWAS. 8th World Congress on Developmental Origins of Health and Disease
    • Place of Presentation
      サンテック国際会議場(シンガポール)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] X染色体不活化関連疾患:エピゲノム異常に起因する. ワークショップ2PW10染色体不活性化のエピジェネティクス.2013

    • Author(s)
      久保田健夫
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] Epigenomics and Epigenetics2014

    • Author(s)
      Kubota T, Miyake K, Hirasawa T.
    • Total Pages
      218
    • Publisher
      Intech (Open Access Publisher)
    • Related Report
      2014 Annual Research Report
  • [Book] Transgenerational Epigenetics: Evidence and Debate2014

    • Author(s)
      Kubota T, Hirasawa T, Miyake K.
    • Total Pages
      396
    • Publisher
      Academic Press
    • Related Report
      2014 Annual Research Report
  • [Remarks] 山梨大学 大学院総合研究部 環境遺伝医学講座

    • URL

      http://www.epigenetmed.com/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 山梨大学医学部環境遺伝医学講座

    • URL

      http://www.epigenetmed.com/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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