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Identification of novel profibrotic cell populations using single cell gene expression analysis and its application to the development of molecular targeted drugs

Research Project

Project/Area Number 19K08652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionThe University of Tokushima

Principal Investigator

KAWANO Hiroshi  徳島大学, 大学院医歯薬学研究部(医学域), 特任准教授 (30771571)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords線維細胞 / 一細胞遺伝子発現解析 / 肺線維症 / 一細胞遺伝子解析 / 細胞接着分子
Outline of Research at the Start

特発性肺線維症は、きわめて予後不良な難治性疾患であり、その分子メカニズムの解明と新たな治療法の開発が求められている。骨髄由来の線維細胞は肺線維症の重要なエフェクター細胞とされるが、特異的な細胞表面マーカーが見つかっておらず生体内での解析が困難であった。最近私たちは、フローサイトメトリーを用いた肺線維細胞の新たな単離方法を開発した。本研究では肺線維細胞の一細胞遺伝子解析を行い、線維細胞の新しい機能的亜集団の同定、線維細胞特異的な細胞表面マーカーの同定、線維細胞の分化調節因子の同定を行う。本研究の成果は、肺線維症に対する新たな疾患バイオマーカー、及び新規分子標的治療薬の開発につながるものである。

Outline of Final Research Achievements

In this study, we performed single cell gene expression analysis of lung fibrocytes to identify new functional subpopulations of fibrocytes, identify novel cell surface markers specific to fibrocytes, and identify regulators of fibrocyte differentiation, with the aim of developing new anti-fibrotic agents based on fibrocyte regulation.
In pulmonary fibrosis model, we isolated a cell population containing fibrocytes using our original method, and performed single cell RNA-seq. We detected subpopulation of macrophages expressing collagen gene. A cell adhesion molecule was identified as cell surface markers specifically expressed in this subpopulation, and their expression kinetics were clarified. We plan to further analyze the functions of the identified adhesion molecules and expand our research to therapeutic applications.

Academic Significance and Societal Importance of the Research Achievements

コラーゲン遺伝子を発現するマクロファージ亜集団は線維細胞を含む可能性が高く、本研究成果は線維細胞特異的マーカーの同定につながる。その後の詳細な線維細胞の機能解析により、肺線維症に対する新たな治療標的分子を同定しうる点で意義、重要性が高いと考えられる。

Report

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

    (1 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Development of improved method to identify and analyze lung fibrocytes with flow cytometry in a reporter mouse strain2020

    • Author(s)
      Kawano Hiroshi、Koyama Kazuya、Nishimura Haruka、Toyoda Yuko、Kagawa Kozo、Sato Seidai、Naito Nobuhito、Goto Hisatsugu、Inagaki Yutaka、Nishioka Yasuhiko
    • Journal Title

      Immunity, Inflammation and Disease

      Volume: 9 Issue: 1 Pages: 120-127

    • DOI

      10.1002/iid3.361

    • NAID

      120007180359

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed

URL: 

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

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