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Identification and Crosstalk of Mesenchymal Cell Subpopulations.

Research Project

Project/Area Number 19K10024
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionJuntendo University (2021-2022)
Tokyo Medical and Dental University (2019-2020)

Principal Investigator

Mabuchi Yo  順天堂大学, 大学院医学研究科, 特任准教授 (50424172)

Co-Investigator(Kenkyū-buntansha) 赤澤 智宏  順天堂大学, 大学院医学研究科, 教授 (80291160)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords間葉系幹細胞 / Single-cell RNA sequence / 細胞多様性 / 細胞間クロストーク / scRNA-Seq / Single-Cell RNA Sequence / 間葉系細胞 / Single-Cell 解析 / 組織幹細胞 / 神経堤細胞 / Single cell RNA sequence
Outline of Research at the Start

間葉系幹細胞は、骨髄をはじめ様々な組織に存在し、生体の恒常性に関与していると考えられている。また間葉系幹細胞は細胞治療の重要なソースとして実用化されており、細胞移植による組織再生効果が確認されている。しかし、治療に関与する細胞集団および因子(細胞成分・液性成分)の同定といった特性解析は進んでいない。本研究では、単一細胞レベルでの遺伝子発現及び表面抗原を指標として間葉系幹細胞を分類することにより、組織修復に関与する因子(再生因子)の特定を行う。

Outline of Final Research Achievements

Mesenchymal stem cells are believed to interact with surrounding cells to contribute to the homeostasis of the organism. However, the heterogeneity of the mesenchymal stem cell population makes it difficult to identify stem cell-specific signals and analyze cell-cell interactions within tissues. In this study, we classified mesenchymal stem cells based on gene expression, which have been treated as a heterogeneous population. As a result, gene expression analysis using mesenchymal stem cell clones revealed that FZD5 is highly expressed in mesenchymal stem cells. Furthermore, using a co-culture experimental system of mesenchymal stem cells and hematopoietic stem cells, we demonstrated that mesenchymal stem cell-secreted factors promote the differentiation of hematopoietic stem cells into bone marrow cells.

Academic Significance and Societal Importance of the Research Achievements

これまでに、レポーターマウス及びリネージトレーシングマウス用いた間葉系幹細胞の可視化や骨髄細胞に対する解析は国内外で進められている。しかしながら、間葉系幹細胞集団の不均一性により、特有のシグナルを同定することが困難であり、培養による性質変化はさらに解析を複雑化する。本研究では、「幹細胞・前駆細胞を含む間葉系細胞亜集団の特性はどのようなものか?」について明らかにし、それぞれ集団を細胞表面抗原と単一細胞による遺伝子発現解析により詳細に定義し、再生治療への関与・細胞間のクロストークを解析する。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 19 results,  Open Access: 19 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] CD73-Positive Cell Spheroid Transplantation Attenuates Colonic Atrophy2023

    • Author(s)
      Hisamatsu Daisuke、Itakura Natsumi、Mabuchi Yo、Ozaki Rion、Suto Eriko Grace、Naraoka Yuna、Ikeda Akari、Ito Lisa、Akazawa Chihiro
    • Journal Title

      Pharmaceutics

      Volume: 15 Issue: 3 Pages: 845-845

    • DOI

      10.3390/pharmaceutics15030845

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles2023

    • Author(s)
      Yamashita Y, Nakada S, Nakamura K, Sakurai H, Ohno K, Goto T, Mabuchi Y, Akazawa C, Hattori N, Arikawa-Hirasawa E.
    • Journal Title

      Biomedicines

      Volume: 11 Issue: 3 Pages: 814-814

    • DOI

      10.3390/biomedicines11030814

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Snai2 and Notch signaling in salivary gland myoepithelial cell fate.2022

    • Author(s)
      Rika Yasuhara, Seya Kang, Tarou Irie, Yo Mabuchi, Satoko Kujiraoka, Akane Yukimori, Shoko Ishida, Junichi Tanaka, Kenji Mishima
    • Journal Title

      Lab Invest.

      Volume: 102(11) Issue: 11 Pages: 1245-1256

    • DOI

      10.1038/s41374-022-00814-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication.2022

    • Author(s)
      Junichi Tanaka, Hidenobu Senpuku, Miho Ogawa, Rika Yasuhara, Shintaro Ohnuma, Koki Takamatsu, Takashi Watanabe, Yo Mabuchi, Shiro Nakamura, Shoko Ishida, Tomohiko Sadaoka, Takashi Takaki, Tatsuo Shirota, Toshikazu Shimane, Tomio Inoue, Takayoshi Sakai, Munemasa Mori, Takashi Tsuji, Ichiro Saito, Kenji Mishima
    • Journal Title

      Nat Cell Biol.

      Volume: 24(11) Issue: 11 Pages: 1595-1605

    • DOI

      10.1038/s41556-022-01007-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hematopoietic-Mesenchymal Signals Regulate the Properties of Mesenchymal Stem Cells2022

    • Author(s)
      Kanazawa Sanshiro、Okada Hiroyuki、Riu Dan、Mabuchi Yo、Akazawa Chihiro、Iwata Junichi、Hoshi Kazuto、Hikita Atsuhiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 15 Pages: 8238-8238

    • DOI

      10.3390/ijms23158238

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis.2022

    • Author(s)
      Hayashi Y, Inoue D, et al.
    • Journal Title

      Cell Reports

      Volume: VOLUME 39, ISSUE 6 Issue: 6 Pages: 110805-110805

    • DOI

      10.1016/j.celrep.2022.110805

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of activated microglia and macrophages by systemically administered DNA/RNA heteroduplex oligonucleotides2022

    • Author(s)
      Nishi Rieko、Ohyagi Masaki、Nagata Tetsuya、Mabuchi Yo、Yokota Takanori
    • Journal Title

      Molecular Therapy

      Volume: 30 Issue: 6 Pages: 2210-2223

    • DOI

      10.1016/j.ymthe.2022.02.019

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Mesenchymal Stem Cell Spheroids with Enhanced Stem Cell Characteristics and Bone Regeneration Ability2022

    • Author(s)
      Ohori-Morita Yumi、Niibe Kunimichi、Limraksasin Phoonsuk、Nattasit Praphawi、Miao Xinchao、Yamada Masahiro、Mabuchi Yo、Matsuzaki Yumi、Egusa Hiroshi
    • Journal Title

      Stem Cells Translational Medicine

      Volume: xx Issue: 4 Pages: 1-16

    • DOI

      10.1093/stcltm/szab030

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and Characterization of Tissue Resident CD29-Positive Progenitor Cells in Livestock to Generate a Three-Dimensional Meat Bud2021

    • Author(s)
      Naraoka Yuna、Mabuchi Yo、Yoneyama Yosuke、Suto Eriko Grace、Hisamatsu Daisuke、Ikeda Mami、Ito Risa、Nakamura Tetsuya、Takebe Takanori、Akazawa Chihiro
    • Journal Title

      Cells

      Volume: 10 Issue: 9 Pages: 2499-2499

    • DOI

      10.3390/cells10092499

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cellular Heterogeneity of Mesenchymal Stem/Stromal Cells in the Bone Marrow2021

    • Author(s)
      Mabuchi Yo、Okawara Chikako、Mendez-Ferrer Simon、Akazawa Chihiro
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 689366-689366

    • DOI

      10.3389/fcell.2021.689366

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells2021

    • Author(s)
      Yamazaki Morio、Sugimoto Kotaro、Mabuchi Yo、Yamashita Rina、Ichikawa-Tomikawa Naoki、Kaneko Tetsuharu、Akazawa Chihiro、Hasegawa Hiroshi、Imura Tetsuya、Chiba Hideki
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 3 Pages: 278-278

    • DOI

      10.3390/biomedicines9030278

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells2020

    • Author(s)
      Harada Seiko、Mabuchi Yo、Kohyama Jun、Shimojo Daisuke、Suzuki Sadafumi、Kawamura Yoshimi、Araki Daisuke、Suyama Takashi、Kajikawa Masunori、Akazawa Chihiro、Okano Hideyuki、Matsuzaki Yumi
    • Journal Title

      STEM CELLS

      Volume: 39 Issue: 3 Pages: 318-330

    • DOI

      10.1002/stem.3317

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Shaking-Culture Method for Generating Bone Marrow Derived Mesenchymal Stromal/Stem Cell-Spheroids With Enhanced Multipotency in vitro2020

    • Author(s)
      Niibe Kunimichi、Ohori-Morita Yumi、Zhang Maolin、Mabuchi Yo、Matsuzaki Yumi、Egusa Hiroshi
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 8 Pages: 590332-590332

    • DOI

      10.3389/fbioe.2020.590332

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advantage of fat-derived CD73 positive cells from multiple human tissues, prospective isolated mesenchymal stromal cells2020

    • Author(s)
      Suto Eriko G.、Mabuchi Yo、Toyota Saki、Taguchi Miyu、Naraoka Yuna、Itakura Natsumi、Matsuoka Yoh、Fujii Yasuhisa、Miyasaka Naoyuki、Akazawa Chihiro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 15073-15073

    • DOI

      10.1038/s41598-020-72012-8

    • NAID

      40022778397

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The extracellular domain of teneurin-4 promotes cell adhesion for oligodendrocyte differentiation2020

    • Author(s)
      Hayashi Chikako、Suzuki Nobuharu、Mabuchi Yo、Kikura Naomi、Hosoda Yukina、de Vega Susana、Akazawa Chihiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 1 Pages: 171-176

    • DOI

      10.1016/j.bbrc.2019.12.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen2019

    • Author(s)
      Ueno Yuta、Fujisaki Keiko、Hosoda Shoko、Amemiya Yusuke、Okazaki Shogo、Notsu Chihiro、Nishiyama Chiharu、Mabuchi Yo、Matsuzaki Yumi、Oda Akihisa、Goitsuka Ryo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20408-20408

    • DOI

      10.1038/s41598-019-56984-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laminin α2, α4, and α5 Chains Positively Regulate Migration and Survival of Oligodendrocyte Precursor Cells2019

    • Author(s)
      Suzuki Nobuharu、Hyodo Mai、Hayashi Chikako、Mabuchi Yo、Sekimoto Kaori、Onchi Chinami、Sekiguchi Kiyotoshi、Akazawa Chihiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19882-19882

    • DOI

      10.1038/s41598-019-56488-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids2019

    • Author(s)
      Ouchi Rie、et al.
    • Journal Title

      Cell Metabolism

      Volume: 30 Issue: 2 Pages: 374-384

    • DOI

      10.1016/j.cmet.2019.05.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sox9 regulates the luminal stem/progenitor cell properties of salivary glands2019

    • Author(s)
      Tanaka Junichi、Mabuchi Yo、Hata Kenji、Yasuhara Rika、Takamatsu Koki、Kujiraoka Satoko、Yukimori Akane、Takakura Ikuko、Sumimoto Hidetoshi、Fukada Toshiyuki、Azuma Masayuki、Akiyama Haruhiko、Nishimura Riko、Shimane Toshikazu、Mishima Kenji
    • Journal Title

      Experimental Cell Research

      Volume: 382 Issue: 1 Pages: 111449-111449

    • DOI

      10.1016/j.yexcr.2019.05.030

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells2020

    • Author(s)
      YO MABUCHI
    • Organizer
      12th Stem Cell Society Singapore Symposium
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 間葉系幹細胞亜集団の同定と特性解析2019

    • Author(s)
      馬渕 洋、須藤 絵里子グレース、鈴木 喜晴、赤澤 智宏
    • Organizer
      第29回日本サイトメトリー学会学術集会
    • Related Report
      2019 Research-status Report
  • [Book] Encyclopedia of Bone Biology.2020

    • Author(s)
      Mabuchi Yo
    • Total Pages
      7
    • Publisher
      Elsevier Inc.
    • ISBN
      9780128140826
    • Related Report
      2020 Research-status Report
  • [Remarks] 順天堂大学 大学院医学研究科 難病の診断と治療研究センター

    • URL

      https://akazawalab.com/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 順天堂大学 大学院医学研究科  難病の診断と治療研究センター

    • URL

      https://akazawalab.com/

    • Related Report
      2021 Research-status Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科分子生命情報解析学分野

    • URL

      http://akazawalab.com/publication/

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 幹細胞の分離方法ならびに培養および分化誘導方法2020

    • Inventor(s)
      赤澤智宏, 須藤絵里子グレース、馬渕洋、武部貴則
    • Industrial Property Rights Holder
      赤澤智宏, 須藤絵里子グレース、馬渕洋、武部貴則
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-079272
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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