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Elucidating expression status of mental illness-related genes, based on single cell analysis of human-postmortem samples

Research Project

Project/Area Number 19K10678
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionGunma University

Principal Investigator

Takahashi Yoichiro  群馬大学, 大学院医学系研究科, 講師 (50640538)

Co-Investigator(Kenkyū-buntansha) 小湊 慶彦  群馬大学, 大学院医学系研究科, 教授 (30205512)
窪 理英子  群馬大学, 医学部, 技術職員 (40747127)
早川 輝  群馬大学, 大学院医学系研究科, 助教 (90758575)
佐野 利恵  群馬大学, 大学院医学系研究科, 准教授 (70455955)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords死後脳 / 精神疾患 / 統合失調症 / 法医学 / 体細胞変異 / 法医解剖 / シングルセル
Outline of Research at the Start

本申請研究は、精神疾患発症のリスク遺伝子について、様々な年齢のヒト死後脳から単一細胞・単一分子レベルで発現量を測定し、遺伝子の時間的・空間的な発現制御についてその仕組みを含めて包括的な理解を得て、精神疾患のメカニズムを解明することを目的とします。本研究の成果は統合失調症等の治療薬開発等に繋がる他、現状では困難である精神疾患の死後診断法の開発を通じて、犯罪捜査や公衆衛生の向上に貢献することが期待されます。

Outline of Final Research Achievements

Using postmortem human brains, the expression pattern of SNX19 and AS3MT, which are genes associated with the development of schizophrenia, was quantitatively evaluated. Especially, the specific splicing variants, SNX19d9 and AS3MTd2d3 that are strongly correlated with risk of schizophrenia, was examined using single molecule in situ hybridization technique. As a result, each transcripts tended to localize specific neuronal cell types. These results suggested that each schizophrenia-related gene is involved in the pathogenesis of psychiatric disorders by disrupting their normal function in a relatively small number of specific cell types.

Academic Significance and Societal Importance of the Research Achievements

統合失調症と関連する遺伝子の発現様態について、ヒト死後脳を解析試料として、一細胞・一分子レベルでの評価を行った。特にSNX19遺伝子とAS3MT遺伝子について解析したところ、これらの遺伝子は共に神経細胞に発現していたが、それぞれが異なった種類の神経細胞で強く発現することが明らかになった。従って、これらの遺伝子異常は比較的限られた種類の神経細胞に異常を引き起こして疾患の発症に関与することが推測された。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (46 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 13 results,  Open Access: 5 results) Presentation (32 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Int'l Joint Research] Lieber Institute for Brain Development(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Usefulness of a tissue optical clearing technique for forensic autopsy2022

    • Author(s)
      Takahashi Yoichiro、Hayakawa Akira、Sano Rie、Fukuda Haruki、Kubo Rieko、Tokue Hiroyuki、Okawa Takafumi、Kawamura Miki、Kominato Yoshihiko
    • Journal Title

      Journal of Forensic Sciences

      Volume: - Issue: 3 Pages: 1124-1131

    • DOI

      10.1111/1556-4029.14995

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of blood group A antigen on erythrocytes in a patient with myelodysplastic syndrome harboring somatic mutations in <i>RUNX1</i> and <i>GATA2</i>2021

    • Author(s)
      Hayakawa Akira、Sano Rie、Takahashi Yoichiro、Okawa Takafumi、Kubo Rieko、Harada Megumi、Fukuda Haruki、Yokohama Akihiko、Handa Hiroshi、Kawabata‐Iwakawa Reika、Tsuneyama Hatsue、Tsukada Junichi、Kominato Yoshihiko
    • Journal Title

      Transfusion

      Volume: 62 Issue: 2 Pages: 469-480

    • DOI

      10.1111/trf.16766

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rupture of segmental dilatation of the sigmoid colon resulting from blunt force to the abdomen in a child2021

    • Author(s)
      Fukuda Haruki、Sano Rie、Hayakawa Akira、Takahashi Yoichiro、Kubo Rieko、Takei Hiroyuki、Awata Sachiko、Tokue Hiroyuki、Kominato Yoshihiko
    • Journal Title

      Forensic Imaging

      Volume: 27 Pages: 200482-200482

    • DOI

      10.1016/j.fri.2021.200482

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the applicability of virtual gastroscopy based on postmortem computed tomography to detect changes in the stomach, along with reports of three rare cases2021

    • Author(s)
      Fukuda Haruki、Sano Rie、Hayakawa Akira、Takahashi Yoichiro、Okawa Takafumi、Kubo Rieko、Takei Hiroyuki、Awata Sachiko、Tokue Hiroyuki、Akuzawa Hisashi、Yuasa Masahiro、Kominato Yoshihiko
    • Journal Title

      Legal Medicine

      Volume: 52 Pages: 101898-101898

    • DOI

      10.1016/j.legalmed.2021.101898

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A cell-specific regulatory region of the human ABO blood group gene regulates the neighborhood gene encoding odorant binding protein 2B.2021

    • Author(s)
      Sano R, Takahashi Y, Fukuda H, Harada M, Hayakawa A, Okawa T, Kubo R, Takeshita H, Tsukada J, Kominato Y.
    • Journal Title

      Scientific Reports

      Volume: Apr 1;11(1) Issue: 1 Pages: 7325-7325

    • DOI

      10.1038/s41598-021-86843-6

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single molecule in situ hybridization reveals distinct localizations of schizophrenia risk-related transcripts SNX19 and AS3MT in human brain2021

    • Author(s)
      Takahashi Yoichiro、Maynard Kristen R.、Tippani Madhavi、Jaffe Andrew E.、Martinowich Keri、Kleinman Joel E.、Weinberger Daniel R.、Hyde Thomas M.
    • Journal Title

      Molecular Psychiatry

      Volume: 26 Issue: 7 Pages: 3536-3547

    • DOI

      10.1038/s41380-021-01046-9

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19.2021

    • Author(s)
      Takahashi Y, Hayakawa A, Sano R, Fukuda H, Harada M, Kubo R, Okawa T, Kominato Y.
    • Journal Title

      Sci Rep.

      Volume: Feb 9;11(1):3379. Issue: 1 Pages: 3379-3379

    • DOI

      10.1038/s41598-021-82970-2

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characteristic postmortem computed tomography findings of ingestion of benzine2021

    • Author(s)
      Tokue Hiroyuki、Kominato Yoshihiko、Sano Rie、Takahashi Yoichiro、Hayakawa Akira、Fukuda Haruki、Tokue Azusa、Tsushima Yoshito
    • Journal Title

      BJR|case reports

      Volume: 66 Issue: 3 Pages: 1148-1153

    • DOI

      10.1259/bjrcr.20200212

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Superimposed CT imaging using fusion function to visualize the relationship between the knife and the wound path in a stabbing victim.2021

    • Author(s)
      Takahashi Y, Sano R, Hayakawa A, Fukuda H, Kubo R, Okawa T, Tokue H, Takei H, Kominato Y.
    • Journal Title

      J Forensic Sci.

      Volume: May;66(3) Issue: 3 Pages: 1148-1153

    • DOI

      10.1111/1556-4029.14653

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues2020

    • Author(s)
      Maynard Kristen R、Tippani Madhavi、Takahashi Yoichiro、Phan BaDoi N、Hyde Thomas M、Jaffe Andrew E、Martinowich Keri
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 11 Pages: e66-e66

    • DOI

      10.1093/nar/gkaa312

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tuberous sclerosis related-lesions detected by postmortem computed tomography2020

    • Author(s)
      Takahashi Yoichiro、Hayakawa Akira、Sano Rie、Fukuda Haruki、Kubo Rieko、Kominato Yoshihiko、Kimura Satoko、Takada Aya、Saito Kazuyuki、Takei Hiroyuki、Awata Sachiko、Tokue Hiroyuki
    • Journal Title

      Forensic Imaging

      Volume: 21 Pages: 200376-200376

    • DOI

      10.1016/j.fri.2020.200376

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human ABO gene transcriptional regulation2020

    • Author(s)
      Kominato Yoshihiko、Sano Rie、Takahashi Yoichiro、Hayakawa Akira、Ogasawara Kenichi
    • Journal Title

      Transfusion

      Volume: 60 Issue: 4 Pages: 860-869

    • DOI

      10.1111/trf.15760

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RUNX1 mutation in a patient with myelodysplastic syndrome and decreased erythrocyte expression of blood group A antigen2019

    • Author(s)
      Hayakawa Akira、Sano Rie、Takahashi Yoichiro、Kubo Rieko、Harada Megumi、Omata Masato、Yokohama Akihiko、Handa Hiroshi、Tsukada Junichi、Takeshita Haruo、Tsuneyama Hatsue、Ogasawara Kenichi、 Kominato Yoshihiko
    • Journal Title

      Transfusion

      Volume: 60 Issue: 1 Pages: 184-196

    • DOI

      10.1111/trf.15628

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨髄異形成症候群におけるABO式血液型抗原量低下の原因解明2021

    • Author(s)
      早川 輝, 佐野利恵, 高橋遥一郎, 大川貴史, 福田治紀, 窪 理英子, 原田 恩, 小湊慶彦
    • Organizer
      日本DNA多型学会第30回学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脊髄損傷を伴う解剖事例における組織透明化手法の有用性の検討2021

    • Author(s)
      高橋遥一郎, 早川 輝, 佐野利恵, 福田治紀, 窪 理英子, 大川貴史, 川村美樹, 小湊慶彦
    • Organizer
      第89回日本法医学会学術関東地方集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] CTフュージョン画像が損傷と成傷器の関係性の描出に有用であった刺創の一例2021

    • Author(s)
      高橋遥一郎, 佐野利恵, 早川輝, 福田治紀, 小湊慶彦
    • Organizer
      第105次日本法医学会学術全国集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ABO遺伝子エンハンサーはOBP2B遺伝子発現を活性化する2021

    • Author(s)
      佐野利恵, 高橋遥一郎, 福田治紀, 早川輝, 窪理英子, 小湊慶彦
    • Organizer
      第105次日本法医学会学術全国集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒストンデアセチラーゼ阻害剤はACE2及びABOの発現を抑制する―COVID-19に対する有用性―2021

    • Author(s)
      高橋遥一郎, 早川輝, 佐野利恵, 福田治紀, 窪理英子, 小湊慶彦
    • Organizer
      第105次日本法医学会学術全国集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Availability of virtual gastroscopy to detect changes in the stomach2021

    • Author(s)
      福田治紀, 佐野利恵, 早川輝, 高橋遥一郎, 窪理英子, 小湊慶彦
    • Organizer
      第105次日本法医学会学術全国集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] An autopsy case of traumatic cerebral infarction due to vascular injury and thromboembolism2021

    • Author(s)
      Hayakawa A, Sano R, Takahashi Y, Fukuda H, Okawa T, Kubo R, Kominato Y
    • Organizer
      24th Congress of the International Academy of Legal Medicine (IALM)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tissue clearing technique allows scanning of the excised spinal cord for microhemorrhages2021

    • Author(s)
      Takahashi Y, Hayakawa A, Sano R, Kubo R, Fukuda H, Okawa T, Kawamura M, Kominato Y
    • Organizer
      第62回日本神経病理学会総会学術研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 刺創における、損傷と成傷器の関係性の描出にCTフュージョン画像を用いた一例.2021

    • Author(s)
      高橋遥一郎,佐野利恵,早川輝,福田治紀,武井宏行,徳江浩之,小湊慶彦.
    • Organizer
      第19回法医画像勉強会/第17回群馬Ai研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 死後CT仮想内視鏡の有用性の検討.2021

    • Author(s)
      福田治紀,佐野利恵,早川輝,高橋遥一郎,窪理英子,小湊慶彦.
    • Organizer
      第19回法医画像勉強会/第17回群馬Ai研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 法医学分野で有用なAi‐CT画像作成のポイント.2021

    • Author(s)
      武井宏行,平澤聡,早川輝,高橋遥一郎,佐野利恵,小湊慶彦.
    • Organizer
      第19回法医画像勉強会/第17回群馬Ai研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] RUNX1 mutation in a patient with myelodysplastic syndrome and decreased erythrocyte expression of blood group A antigen.2020

    • Author(s)
      Hayakawa A, Sano R, Takahashi Y, Fukuda H, Yokohama A, Handa H, Tsuneyama H, Ogasawara K, Kominato Y.
    • Organizer
      The 36th International congress of the International Society of Blood Transfusion (ISBT)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ABO遺伝子エンハンサーはOBP2B遺伝子発現を活性化する.2020

    • Author(s)
      佐野利恵,福田治紀,高橋遥一郎,早川輝,窪理英子,小湊慶彦.
    • Organizer
      日本DNA多型学会第29回学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 死後画像検査の結節性硬化症における有用性の検討.2020

    • Author(s)
      高橋遥一郎,早川輝,佐野利恵,福田治紀,木村聡子,髙田綾,齋藤一之,小湊慶彦.
    • Organizer
      第89回日本法医学会学術関東地方集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 死後脳研究を礎として精神疾患の分子基盤解明を目指す.2020

    • Author(s)
      高橋遥一郎.
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 死後CT仮想内視鏡を用いた消化管内検索の有用性.2020

    • Author(s)
      福田治紀,佐野利恵,早川輝,高橋遥一郎,窪理英子,小湊慶彦.
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 死後変化が進行する心臓に対して死後CT血管造影検査が有用であった一例.2020

    • Author(s)
      高橋遥一郎,早川輝,佐野利恵,福田治紀,小湊慶彦.
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
  • [Presentation] ABO式血液型判定でみられるmixed field agglutinationは血液型亜型か?それとも骨髄悪性疾患か?2020

    • Author(s)
      佐野利恵,早川輝,高橋遥一郎,福田治紀,窪理英子,小湊慶彦.
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 冠状動脈起始部位・走行異常(AAOLCA-IA)に合併した、StanfordA型急性大動脈解離の一剖検例.2020

    • Author(s)
      早川輝,氣賀澤秀明,木村聡子,斎藤一之,高橋遥一郎,佐野利恵,福田治紀,窪理英子,小湊慶彦.
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
  • [Presentation] ABO式血液型判定でみられるmixed field agglutination における血液型亜型と造血器腫瘍の違い.2020

    • Author(s)
      横濱章彦,西本奈津美,岩原かなえ,石川怜依奈,須佐梢,丸橋隆行,関上智美,早川輝,高橋遥一郎,佐野利恵,小湊慶彦.
    • Organizer
      第68回日本輸血・細胞治療学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Evaluation of the cell type-specific expression of schizophrenia risk-related transcripts in postmortem human dorsolateral prefrontal cortex using single molecule in situ hybridization2019

    • Author(s)
      Takahashi Y, Maynard KR, Tippani M, Jaffe AE, Martinowich K, Weinberger DR, Hyde TM.
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dotdotdot - automated workflow for quantification and analysis of RNA transcripts in individual nuclei.2019

    • Author(s)
      Tippani M, Maynard KR, Takahashi Y, Phan B, Weinberger DR, Hyde TM, Martinowich K, Jaffe AE.
    • Organizer
      BioImage Informatics 2019.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ABO式血液型判定でみられるmixed field agglutinationは血液型亜型か?それとも骨髄悪性疾患か?2019

    • Author(s)
      佐野利恵,早川輝,高橋遥一郎,窪理英子,小湊慶彦.
    • Organizer
      日本DNA多型学会第28回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ABO式血液型判定でみられるmixed field agglutinationは血液型亜型か?それとも骨髄悪性疾患か?2019

    • Author(s)
      佐野利恵,早川輝,高橋遥一郎,横濱章彦,小湊慶彦.
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 結節性硬化症2例における死後画像検査の有用性の検討.2019

    • Author(s)
      高橋遥一郎, 早川輝, 佐野利恵, 木村聡子, 髙田綾, 齋藤一之, 小湊慶彦.
    • Organizer
      第88回日本法医学会学術関東地方集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨髄異形成症候群の一患者におけるABO式血液型抗原量低下の原因解明.2019

    • Author(s)
      佐野利恵,早川輝,高橋遥一郎,横濱章彦,半田寛,塚田順一,小笠原健一,小湊慶彦.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨髄異形成症候群の一患者におけるABO式血液型抗原量低下の原因解明.2019

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,小湊慶彦,半田寛,丸橋隆行,横濱章彦.
    • Organizer
      第66回北関東医学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 交通事故受傷後2日後に突然心肺停止となった外傷性脳梗塞の1剖検例.2019

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,小湊慶彦.
    • Organizer
      第2回日本法医病理学会学術全国集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨髄異形成症候群の一患者におけるABO式血液型抗原量低下の原因解明.2019

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,窪理英子,小湊慶彦.
    • Organizer
      第103次日本法医学会学術全国集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 死後CT検査において見出された刺青のイメージ.2019

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,小湊慶彦.
    • Organizer
      第103次日本法医学会学術全国集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨髄異形成症候群の一患者におけるABO式血液型抗原量低下の原因解明.2019

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,丸橋隆行,横濱章彦,半田寛,常山初江,小笠原健一,小湊慶彦.
    • Organizer
      第67回日本輸血・細胞治療学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Tattoo image composed of radiopaque deposits demonstrated by postmortem computed tomography.2019

    • Author(s)
      Hayakawa A, Sano R, Takahashi Y, Akuzawa H, Kominato Y.
    • Organizer
      The 8th Congress of the International Society of Forensic Radiology and Imaging (ISFRI2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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