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Latent variable models of multilayer epigenetic information of neurons for memory

Research Project

Project/Area Number 22K19823
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 62:Applied informatics and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kishi Yusuke  東京大学, 定量生命科学研究所, 准教授 (00645236)

Co-Investigator(Kenkyū-buntansha) 水野 忠快  東京大学, 大学院薬学系研究科(薬学部), 助教 (90736050)
Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsニューロン / エピゲノム / 潜在変数モデル / 老化 / テンソル分解 / エピジェネティクス
Outline of Research at the Start

記憶の実体は人類の最大の謎の1つである。本研究では、幼少期にストレスを与えたマウスをモデルとして、ニューロンのエピジェネティクス情報を潜在変数モデルにより解析することで、個体の記憶の実体を解明することを目指す。そのため、幼少期ストレスを与えたマウスの海馬から採取したニューロン核を用いて包括的にエピジェネティクス情報を取得する。そして、それを複数の解析手法にて因子構造を推定し、幼少期ストレスの有無を最も区別できる方法論を確立することで、幼少期ストレスの記憶を読み取る。これにより、将来的にはこの方法論を用いて個体の記憶の読み取りと、その分子生物学的操作により記憶の書き換えが可能になると期待される。

Outline of Final Research Achievements

What makes me who I am is memory, and the substance of memory is one of our greatest mysteries. We focused on the epigenetic information of neurons. The same genetic information is encoded in the genome of every cell in the body, but epigenetics is important for each cell type to acquire different properties. Therefore, it is the 'marker' that determines which genes can be read (transcribed) in a cell, and this varies from cell to cell.
This study tested the hypothesis that epigenetic information in neurons records individual memories in a different layers to previous studies, such as synaptic connections, and showed that the experiences of mice, such as aging, were recorded into the epigenetic information.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、潜在変数モデルを用いた解析によりニューロンのエピジェネティクスに過去の経験が書き込まれていることが明らかとなった。そのため、エピゲノムを操作することにより、ストレスや疾患といった環境変化によるニューロンの状態を変化させ、脳機能を改善することができる可能性がある。今後は、ニューロンエピジェネティクスを用いた脳機能の回復について研究を進めていきたい。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (25 results)

All 2024 2023 2022 2020 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 5 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Remarks (1 results)

  • [Journal Article] Miyoshi G, Ueta Y, Yagasaki Y, Kishi Y, Fishell G, Machold RP, Miyata M2024

    • Author(s)
      Developmental trajectories of GABAergic cortical interneurons are sequentially modulated by dynamic FoxG1 expression level
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 121 Issue: 16

    • DOI

      10.1073/pnas.2317783121

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Frey T, Murakami T, Maki K, Kawaue T, Tani N, Sugai A, Nakazawa N, Ishiguro K, Adachi T, Kengaku M, Ohki K, Gotoh Y & Kishi Y2023

    • Author(s)
      Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex
    • Journal Title

      Aging Cell

      Volume: 22 Issue: 9 Pages: 1-14

    • DOI

      10.1111/acel.13925

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HMGA2 directly mediates chromatin condensation in association with neuronal fate regulation2023

    • Author(s)
      Kuwayama Naohiro、Kujirai Tomoya、Kishi Yusuke、Hirano Rina、Echigoya Kenta、Fang Lingyan、Watanabe Sugiko、Nakao Mitsuyoshi、Suzuki Yutaka、Ishiguro Kei-ichiro、Kurumizaka Hitoshi、Gotoh Yukiko
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 6420-6420

    • DOI

      10.1038/s41467-023-42094-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UTX deficiency in neural stem/progenitor cells results in impaired neural development, fetal ventriculomegaly, and postnatal death2022

    • Author(s)
      Koizumi M, Eto H, Saeki M, Seki M, Fukushima T, Mukai S, Ide H, Sera Y, Iwasaki M, Suzuki Y, Tohei A, Kishi Y, Honda H.
    • Journal Title

      FASEB journal

      Volume: 36(12) Issue: 12 Pages: 22662-22662

    • DOI

      10.1096/fj.202201002rr

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex2022

    • Author(s)
      Tanita Frey, Tomonari Murakami, Koichiro Maki, Takumi Kawaue, Ayaka Sugai, Naotaka Nakazawa, Taiji Adachi, Mineko Kengaku, Kenichi Ohki, Yukiko Gotoh, Yusuke Kishi
    • Journal Title

      bioRxiv

      Volume: - Pages: 504704-504704

    • DOI

      10.1101/2022.08.22.504704

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] In utero gene transfer system for embryos before neural tube closure reveals a role for Hmga2 in the onset of neurogenesis2020

    • Author(s)
      Naohiro Kuwayama, Yusuke Kishi*, Yurie Maeda, Yurie Nishiumi, Yutaka Suzuki, Haruhiko Koseki, Yusuke Hirabayashi, Yukiko Gotoh (*Correspondence)
    • Journal Title

      bioRxiv

      Volume: - Pages: 086330-086330

    • DOI

      10.1101/2020.05.14.086330

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Presentation] ALTERATIONS IN TRANSCRIPTOME AND CHROMATIN ACCESSIBILITY OF NEURONAL SUBTYPES IN AGED HIPPOCAMPUS.2024

    • Author(s)
      Merve Bilgic, Yukiko Gotoh, Yusuke Kishi
    • Organizer
      第41回 染色体ワークショップ・第22回 核ダイナミクス研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 老齢脳における遺伝子発現の単一細胞プロファイルで明らかにするミクログリアの不均一 性2024

    • Author(s)
      菅井 彩香, Merve Bilgic, 後藤 由季子, 岸 雄介
    • Organizer
      第41回 染色体ワークショップ・第22回 核ダイナミクス研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ニューロンにおけるエピゲノムの役割2024

    • Author(s)
      岸 雄介
    • Organizer
      学術変革3領域(グリアデコード・臨界期生物学・適応回路センサス)合同シンポジウム「細胞多様性-回路多様性-機能多様性」
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The role of the epigenome in neuronal aging2023

    • Author(s)
      Yusuke Kishi, Mai Saeki, YukikoGotoh
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ALTERATIONS IN TRANSCRIPTOME AND CHROMATIN ACCESSIBILITY OF NEURONAL SUBTYPES IN AGED HIPPOCAMPUS.2023

    • Author(s)
      Merve Bilgic, Yukiko Gotoh, Yusuke Kishi
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 老化脳における遺伝子発現の単一細胞プロファイルで明らかにするミクログリアの不均一性2023

    • Author(s)
      Ayaka Sugai, Merve Bilgic, Yukiko Gotoh, Yusuke Kishi
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ニューロンの老化における抑制性エピゲノム変化の解析2023

    • Author(s)
      岸 雄介, 佐伯 麻衣, Merve Bilgic, 後藤 由季子
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ニューロンにおける核ダイナミクス2023

    • Author(s)
      岸 雄介, Tanita Frey, 長田 侑, 牧 功一郎, 安達 泰治, 後藤 由季子
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 老化脳における遺伝子発現の単一細胞プロファイルで明らかにするミクログリアの不均一性2023

    • Author(s)
      菅井 彩香, Merve Bilgic, 後藤 由季子, 岸 雄介
    • Organizer
      BioUT
    • Related Report
      2023 Annual Research Report
  • [Presentation] The role of epigenome in neuronal aging2023

    • Author(s)
      Yusuke Kishi, Mai Saeki, Yukiko Gotoh
    • Organizer
      The 16th Annual Meeting and Korea-Japan Joint Meeting for Developmental Neuroscientists
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of complex brain development by single-cell transcriptome profiling of ferret neural progenitors2023

    • Author(s)
      Merve Bilgic、Fumio Matsuzaki
    • Organizer
      The 16th Annual Meeting and Korea-Japan Joint Meeting for Developmental Neuroscientists
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] ニューロン老化におけるエピゲノムの役割の解明2022

    • Author(s)
      岸雄介、佐伯麻衣、Merve Bilgic、後藤由季子
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] ニューロン老化におけるエピゲノムの役割2022

    • Author(s)
      岸雄介、佐伯麻衣、Merve Bilgic、後藤由季子
    • Organizer
      新学術・学術変革領域合同若手の会
    • Related Report
      2022 Research-status Report
  • [Presentation] ALTERATIONS IN TRANSCRIPTOME AND CHROMATIN ACCESSIBILITY OF NEURONAL SUBTYPES IN AGED HIPPOCAMPUS2022

    • Author(s)
      Merve Bilgic、後藤由季子、岸雄介
    • Organizer
      新学術・学術変革領域合同若手の会
    • Related Report
      2022 Research-status Report
  • [Presentation] 老齢マイクログリアにおける転写プロファイルの不均一性の解析2022

    • Author(s)
      菅井彩香、Merve Bilgic、後藤由季子、岸雄介
    • Organizer
      新学術・学術変革領域合同若手の会
    • Related Report
      2022 Research-status Report
  • [Presentation] Alterations in transcriptome and chromatin accessibility of neuronal subtypes in aged hippocampus2022

    • Author(s)
      Merve Bilgic、後藤由季子、岸雄介
    • Organizer
      The Transcription, Chromatin, and Epigenetics in Aging Conference
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dynamic changes in the chromatin and nuclear state during neuronal differentiation ニューロン分化過程におけるクロマチンと核の変化2022

    • Author(s)
      岸雄介、佐伯麻衣、後藤由季子
    • Organizer
      55th Annual Meeting of the Japanese Society of Developomental Biologists
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Nuclear morphology of cortical excitatory neurons is regulated by visual experience and aging2022

    • Author(s)
      Tanita M. Frey, Tomonari Murakami, Kenichi Ohki, Yukiko Gotoh, Yusuke Kishi
    • Organizer
      Society for Neuroscience 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] ニューロンの核は老化するとシワシワになり、かたくなる

    • URL

      https://www.iqb.u-tokyo.ac.jp/pressrelease/230725/

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2022-07-05   Modified: 2025-01-30  

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