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Establishment of a research platform for studying CNS macrophages

Research Project

Project/Area Number 20K22687
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0704:Neuroscience, brain sciences, and related fields
Research InstitutionKyushu University

Principal Investigator

Masuda Takahiro  九州大学, 薬学研究院, 准教授 (80615287)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsミクログリア / 脳境界マクロファージ / 中枢神経系疾患 / 脳 / 遺伝子改変マウス / 中枢神経系マクロファージ / Hexb / マウス
Outline of Research at the Start

脳および脊髄を含む中枢神経系組織には、実質に存在するミクログリア細胞に加え、境界領域に種類の異なるマクロファージ[CNS-associated macrophages(CAMs)]が存在する。本研究では、以下2項目 (1) シングルセルトランスクリプトーム解析技術を用いたミクログリアおよびCAMsの遺伝子発現プロファイルの包括的比較解析によるミクログリア特異的遺伝子の特定、 (2) ミクログリア特異的遺伝子のプロモーターを用いた細胞種特異的遺伝子改変マウスの作成およびその機能解析を進め、ミクログリアおよびCAMsの機能解明に向けた研究基盤の創出を目指す。

Outline of Final Research Achievements

The central nervous system (CNS) hosts a variety of innate immune cells including macrophages, which are found either in the parenchyma, called microglia, or at the CNS interfaces, such as leptomeningeal, and perivascular macrophages (CNS-associated macrophages). To date, little is known about their cell-type-specific roles in the absence of suitable tools, allowing for functional discrimination between microglia and CNS-associated macrophages. To develop a new microglia gene targeting model, we first applied single-cell RNA-sequencing to identify a stably expressed microglia core geneduring homeostasis and disease. Then, we generated novel mouse lines taht specifically target microglia. In summary, our novel genetic tools will provide a valuable option to study microglia functions in the CNS.

Academic Significance and Societal Importance of the Research Achievements

ミクログリアおよび脳境界マクロファージは、その発生メカニズムおよび遺伝子発現プロファイルに類似性が認められ、現存する遺伝子改変マウスではそれらを正確に分けて生理学的および病態生理学的な機能を解析することは難しい。そのため、これまで“ミクログリアが関与する”と考えられてきた中枢性応答や疾患発症メカニズムにおいて、実はその役割がほとんど分かっていない脳境界マクロファージが重要な役割を担っている可能性も十分にある。そのため、本研究により開発された新規細胞機能操作ツールは、今後ミクログリアと脳境界マクロファージを区別して詳細な機能解明を進めていく過程において非常に有用なツールになると考えられる。

Report

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

    (19 results)

All 2022 2021 2020 Other

All Int'l Joint Research (7 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (8 results) (of which Invited: 3 results)

  • [Int'l Joint Research] University of Freiburg/University of Leipzig/Max Planck Institute(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Karolinska Institute/Uppsala University(スウェーデン)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Paris(フランス)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Edinburgh and UK DRI(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Freiburg(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Weizmann Institute of Science(イスラエル)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Specification of CNS macrophage subsets occurs postnatally in defined niches.2022

    • Author(s)
      Masuda T,Amann L,Monaco G,Sankowski R,Staszewski O,Krueger M,Gaudio FD,He L,Paterson N,Nent E,Fernandez-Klett F,Yamasaki A,Frosch M,Fliegauf M,Bosch LFP,Ulupinar H,Hagemeyer N,Schreiner D,Dorrier C,Tsuda M,Grothe C,Joutel A,Daneman R,Betsholtz C,Lendahl U,Knobeloch KP,Laemmermann T,Priller J,Kierdorf K,Prinz M
    • Journal Title

      Nature

      Volume: in press

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A spinal microglia population involved in remitting and relapsing neuropathic pain2022

    • Author(s)
      Kohno Keita、Shirasaka Ryoji、Yoshihara Kohei、Mikuriya Satsuki、Tanaka Kaori、Takanami Keiko、Inoue Kazuhide、Sakamoto Hirotaka、Ohkawa Yasuyuki、Masuda Takahiro、Tsuda Makoto
    • Journal Title

      Science

      Volume: 376 Issue: 6588 Pages: 86-90

    • DOI

      10.1126/science.abf6805

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microglia and Central Nervous System?Associated Macrophages?From Origin to Disease Modulation2021

    • Author(s)
      Prinz Marco、Masuda Takahiro、Wheeler Michael A.、Quintana Francisco J.
    • Journal Title

      Annual Review of Immunology

      Volume: 39 Issue: 1 Pages: 251-277

    • DOI

      10.1146/annurev-immunol-093019-110159

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel Hexb-based tools for studying microglia in the CNS2020

    • Author(s)
      Masuda Takahiro、Amann Lukas、Sankowski Roman、Staszewski Ori、Lenz Maximilian、d´Errico Paolo、Snaidero Nicolas、Costa Jord?o Marta Joana、B?ttcher Chotima、Kierdorf Katrin、Jung Steffen、Priller Josef、Misgeld Thomas、Vlachos Andreas、Meyer-Luehmann Melanie、Knobeloch Klaus-Peter、Prinz Marco
    • Journal Title

      Nature Immunology

      Volume: 21 Issue: 7 Pages: 802-815

    • DOI

      10.1038/s41590-020-0707-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 多様な脳内マクロファージと治療標的としての可能性2022

    • Author(s)
      増田隆博
    • Organizer
      第2回SAMURAI研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Cellular and molecular heterogeneity of CNS macrophages in health and disease2022

    • Author(s)
      増田隆博
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Decoding brain environment through single-cell analysis of microglia2022

    • Author(s)
      増田隆博
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ミクログリアという小さな細胞の多彩な能力2021

    • Author(s)
      増田隆博
    • Organizer
      脳科学若手の会 第24回談話会「Microglia」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウスおよびヒト脳内におけるミクログリアの多様性および可塑性2021

    • Author(s)
      増田隆博
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Diversity and plasticity of microglia in mouse and human brains2021

    • Author(s)
      増田隆博
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脳実質ミクログリアと脳境界マクロファージ2021

    • Author(s)
      増田隆博
    • Organizer
      第43回日本疼痛学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Single-cell analysis reveals spatial and temporal heterogeneity of microglia in human and mice2020

    • Author(s)
      Takahiro Masuda
    • Organizer
      第63回 日本神経化学会大会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-09-29   Modified: 2023-01-30  

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