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Identification and characterization of skeletal stem cells by spatio-temporal transcriptomics

Research Project

Project/Area Number 21K19596
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionOsaka University

Principal Investigator

Hata Kenji  大阪大学, 大学院歯学研究科, 准教授 (80444496)

Co-Investigator(Kenkyū-buntansha) 宇佐美 悠  大阪大学, 大学院歯学研究科, 講師 (80444579)
奥崎 大介  大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (00346131)
Project Period (FY) 2021-07-09 – 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: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords幹細胞 / 骨格形成 / 骨格系幹細胞 / シングルセル解析 / 骨格系細胞
Outline of Research at the Start

骨格形成や骨・軟骨の再生において中心的役割を担う骨芽細胞および軟骨細胞は、骨格系幹細胞をその起源とする。したがって、骨格形成の分子メカニズムの理解やそれを基盤とする効率的な骨・軟骨再生法の確立には、骨格系幹細胞の細胞特性や分化制御機構の解明がカギとなる。本研究では、1細胞レベルでの時間的遺伝子発現解析と空間的な遺伝子発現解析を統合することで、骨組織の時空間的トランスクリプトミクスを行い、骨格系幹細胞のマーカー遺伝子の同定と持続的維持機構の解明に挑戦する。さらに、骨格系幹細胞から軟骨細胞および骨芽細胞への分化の分岐点を制御する遺伝子ネットワークを明らかにすることを目指す。

Outline of Final Research Achievements

Skeletal stem cells are the cell population which are the origin of chondrocytes and osteoblasts and they play important roles in skeletal development. In this study, we applied single-cell genomic technology to the study of skeletal stem cells and analyzed the cell population of bone tissue using spatio-temporal transcrimtomics. We performed scRNA-seq analysis using bone tissues and identified differentially expressed genes in the cluster of skeletal stem cells. Furthermore, we found that transcription factors specifically expressed in skeletal stem cells promote the expression of multiple Wnt genes. These findings suggest that skeletal stem cells regulate skeletal development through Wnt signaling.

Academic Significance and Societal Importance of the Research Achievements

本研究は、最先端のシングルセルゲノミクスを駆使して、未だ解明されていない骨格系幹細胞の細胞特性の解明を目指す研究である。現在まで本研究のように骨格系幹細胞を時空的に解析する研究アプローチは見られないことから、新規性の高い研究結果が得られると考えられる。骨格系幹細胞は骨格形成のみならず骨・軟骨再生における骨芽細胞/軟骨細胞の供給源であり、本研究で同定する骨格系幹細胞マーカー遺伝子は、骨・軟骨形成能の高い幹細胞の採取にきわめて有用である。したがって、本研究は骨・軟骨再生のための科学的基盤を創出し、骨・軟骨疾患治療にも貢献すると期待され、挑戦的研究としての波及効果は高い。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 Other

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

  • [Int'l Joint Research] UC Denver(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] HOXA10 promotes Gdf5 expression in articular chondrocytes2023

    • Author(s)
      Murakami Tomohiko、Ruengsinpinya Lerdluck、Takahata Yoshifumi、Nakaminami Yuri、Hata Kenji、Nishimura Riko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-023-50318-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory Mechanisms of Prg4 and Gdf5 Expression in Articular Cartilage and Functions in Osteoarthritis2022

    • Author(s)
      Takahata Yoshifumi, Hagino Hiromasa, Kimura Ayaka, Urushizaki Mitsuki, Yamamoto Shiori, Wakamori Kanta, Murakami Tomohiko, Hata Kenji, Nishimura Riko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 9 Pages: 4672-4672

    • DOI

      10.3390/ijms23094672

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx22021

    • Author(s)
      Takahata Yoshifumi、Hagino Hiromasa、Kimura Ayaka、Urushizaki Mitsuki、Kobayashi Sachi、Wakamori Kanta、Fujiwara Chika、Nakamura Eriko、Yu Kayon、Kiyonari Hiroshi、Bando Kana、Murakami Tomohiko、Komori Toshihisa、Hata Kenji、Nishimura Riko
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1199-1199

    • DOI

      10.1038/s42003-021-02717-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice2021

    • Author(s)
      Nakamura Eriko、Hata Kenji、Takahata Yoshifumi、Kurosaka Hiroshi、Abe Makoto、Abe Takaya、Kihara Miho、Komori Toshihisa、Kobayashi Sachi、Murakami Tomohiko、Inubushi Toshihiro、Yamashiro Takashi、Yamamoto Shiori、Akiyama Haruhiko、Kawaguchi Makoto、Sakata Nobuo、Nishimura Riko
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1258-1258

    • DOI

      10.1038/s42003-021-02793-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 軟骨細胞分化における高次遺伝子発現制御機構の解明2023

    • Author(s)
      波多賢二
    • Organizer
      第41回日本骨代謝学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Transcriptional control of skeletal development2023

    • Author(s)
      Kenji Hata
    • Organizer
      71st Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of Chondrocyte-specific Sox9 Enhancers Important for Skeletal Development2022

    • Author(s)
      Hata K, Kobayash S, Takahata Y, Murakami T, Nishimura R
    • Organizer
      Japan Bone Academy 2022
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Transcriptional control of skeletal development2022

    • Author(s)
      Hata K
    • Organizer
      第20回松山国際学術シンポジウム
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Dmrt2 promotes transition of endochondral ossification by linking Sox9 and Runx22021

    • Author(s)
      K. Hata, K. Ono, E. Nakamura, S. Kobayashi, Y. Takahata, T. Murakami, R. Nishimura.
    • Organizer
      2021 ECTS Digital Congress
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 軟骨細胞におけるSox9遺伝子の発現制御機構の解明2021

    • Author(s)
      小林 紗知, 波多 賢二, 高畑 佳史,村上 智彦,高野 洋志,八尾良司, 鵜澤 成一, 西村 理行
    • Organizer
      第6回日本骨免疫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 軟骨細胞におけるSox9遺伝子のエンハンサー領域の同定と機能解析2021

    • Author(s)
      小林 紗知, 波多 賢二, 高畑 佳史,村上 智彦,西村 理行
    • Organizer
      第39回日本骨代謝学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Identification of Chondrocyte-specific Sox9 Enhancers Important for Skeletal Development2021

    • Author(s)
      S. Kobayashi, K. Hata,Y. Takahata, T. Murakami, N.Uzawa,R. Nishimura
    • Organizer
      米国骨代謝学会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Book] 最新の骨粗鬆症学(第二版)「サイトカイン」2022

    • Author(s)
      波多賢二
    • Total Pages
      667
    • Publisher
      日本臨床社
    • Related Report
      2022 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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