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Elucidation of bone marrow stromal cell function using single cell analysis

Research Project

Project/Area Number 19K19236
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionNagasaki University

Principal Investigator

Matsushita Yuki  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (00713827)

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 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords軟骨原基 / 傍軟骨膜 / 骨髄間質細胞 / 細胞系譜追跡 / シングルセル解析
Outline of Research at the Start

成体における骨髄間質細胞は、間葉系幹細胞としての機能を有しており、骨芽細胞をはじめとする間葉系細胞に分化することで、骨折などの損傷時の組織再生に寄与する。骨髄間質細胞は胎生期の間葉系凝集やその周囲の軟骨膜の細胞に由来すると言われているが、その詳細な分化過程は明らかにされていない。今回申請者は、間葉系凝集由来および軟骨膜由来の骨髄間質細胞が生体骨髄において異なる機能を果たすという仮説を立て、それぞれに由来する細胞をタモキシフェン誘導性に時期特異的に標識するCreERマウスを用い、一細胞レベルでのゲノムワイドな網羅的解析を行いこれらの骨髄間質細胞の基本的な性質を明らかにする。

Outline of Final Research Achievements

Bone marrow stromal cells in the adult body function as mesenchymal stem cells and contribute to tissue regeneration at the time of fracture or other injury by differentiating into osteoblasts and other mesenchymal cells. Bone marrow stromal cells are said to originate from embryonic mesenchymal condensations and cells of the surrounding perichondrium, but it has not been clarified how cells of these different origins contribute to the diversity of bone marrow stromal cell populations. In this study, we used cell lineage tracing to elucidate the process by which cells constituting the embryonic cartilage temlate and surrounding perichondrial cells form the skeletal system. The diversity of the bone marrow stromal cells ultimately constituted was also elucidated, as well as their developmental origins.

Academic Significance and Societal Importance of the Research Achievements

近年のシングルセル解析の発展により、骨髄間質細胞を含む骨格系細胞の多様性の解析が進んでいる。しかしながら、骨髄間葉系幹細胞の候補と言われている骨髄間質細胞についてはその起源は正確には分かっていなかった。本研究成果により、骨髄間質細胞の二つの起源となる細胞が明らかになった。このことにより、骨格の発生、成長過程における、細胞の系譜が明らかとなり、発生生物学研究や幹細胞研究の発展に寄与する。

Report

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

    (16 results)

All 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] University of Michigan/UT Health Science Center(米国)

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

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Michigan/Harvard University/Washington University(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow2021

    • Author(s)
      Matsushita Yuki、Chu Angel Ka Yan、Ono Wanida、Welch Joshua D、Ono Noriaki
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 36 Issue: 6 Pages: 1145-1158

    • DOI

      10.1002/jbmr.4282

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Flow Cytometry-Based Analysis of the Mouse Bone Marrow Stromal and Perivascular Compartment2021

    • Author(s)
      Matsushita Yuki、Ono Wanida、Ono Noriaki
    • Journal Title

      Methods in Molecular Biology

      Volume: 2308 Pages: 83-94

    • DOI

      10.1007/978-1-0716-1425-9_7

    • ISBN
      9781071614242, 9781071614259
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration.2020

    • Author(s)
      Matsushita, Y., Nagata, M., Kozloff, K.M., Welch, J.D., Mizuhashi, K., Tokavanich, N., Hallett, S.A., Link, D.C., Nagasawa, T., Ono, W., and Ono, N*.
    • Journal Title

      Nat Commun.

      Volume: 11 Issue: 1 Pages: 332-332

    • DOI

      10.1038/s41467-019-14029-w

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Growth plate skeletal stem cells and their transition from cartilage to bone2020

    • Author(s)
      Matsushita Yuki、Ono Wanida、Ono Noriaki
    • Journal Title

      Bone

      Volume: 136 Pages: 115359-115359

    • DOI

      10.1016/j.bone.2020.115359

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Skeletal Stem Cells for Bone Development and Repair: Diversity Matters2020

    • Author(s)
      Matsushita Yuki、Ono Wanida、Ono Noriaki
    • Journal Title

      Current Osteoporosis Reports

      Volume: 18 Issue: 3 Pages: 189-198

    • DOI

      10.1007/s11914-020-00572-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A three-dimensional analysis of primary failure of eruption in humans and mice.2020

    • Author(s)
      5)Tokavanich N, Gupta A, Nagata M, Takahashi A, Matsushita Y, Yatabe M, Ruellas A, Cevidanes L, Maki K, Yamaguchi T, Ono N, Ono W.
    • Journal Title

      Oral Dis

      Volume: 26 Issue: 2 Pages: 391-400

    • DOI

      10.1111/odi.13249

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Microsurgical Anatomy of the Superior Wall of the Mandibular Canal and Surrounding Structures: Suggestion for New Classifications for Dental Implantology2019

    • Author(s)
      Iwanaga Joe、Anand Mahindra Kumar、Jain Mitesh N.、Nagata Mizuki、Matsushita Yuki、Ibaragi Soichiro、Kusukawa Jingo、Tubbs R. Shane
    • Journal Title

      Clinical Anatomy

      Volume: 33 Issue: 2 Pages: 223-231

    • DOI

      10.1002/ca.23456

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration2019

    • Author(s)
      Pepe-Mooney Brian J.、Dill Michael T.、Alemany Anna、Ordovas-Montanes Jose、Matsushita Yuki、Rao Anuradha、Sen Anushna、Miyazaki Makoto、Anakk Sayeepriyadarshini、Dawson Paul A.、Ono Noriaki、Shalek Alex K.、van Oudenaarden Alexander、Camargo Fernando D.
    • Journal Title

      Cell Stem Cell

      Volume: 25 Issue: 1 Pages: 23-38.e8

    • DOI

      10.1016/j.stem.2019.04.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Growth Plate Borderline Chondrocytes Behave as Transient Mesenchymal Precursor Cells2019

    • Author(s)
      Mizuhashi Koji、Nagata Mizuki、Matsushita Yuki、Ono Wanida、Ono Noriaki
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 34 Issue: 8 Pages: 1387-1392

    • DOI

      10.1002/jbmr.3719

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Distinct cellular origins of the fetal cartilage dictate bone marrow stromal cell heterogeneity2021

    • Author(s)
      Matsushita Yuki、Ono Noriaki
    • Organizer
      American Society for Bone and Mineral Research, 43th Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Notch effector Hes1 marks early perichondrial progenitor cells in endochondral bone development2020

    • Author(s)
      Matsushita Yuki、Ono Noriaki
    • Organizer
      Gordon Research Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Notch effector Hes1 marks early perichondrial progenitor cells in endochondral bone development2020

    • Author(s)
      Matsushita Yuki、Ono Noriaki
    • Organizer
      Gordon Research Seminar
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Single-cell analysis unveils unique cell plasticity of native bone marrow stromal cells in bone regeneration2019

    • Author(s)
      Matsushita Yuki、Ono Noriaki
    • Organizer
      American Society for Bone and Mineral Research, 41st Annual Meeting
    • 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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