Single-cell analysis of mesenchymal stem/stromal cells across mouse limbs.

• Project/Area Number: 18KK0449
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Juntendo University (2021-2022); Tokyo Medical and Dental University (2018-2020)
• Principal Investigator: Mabuchi Yo 順天堂大学, 大学院医学研究科, 特任准教授 (50424172)
• Project Period (FY): 2019 – 2022
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• 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 / 単一細胞解析

Outline of Final Research Achievements

In this study, we conducted an analysis of subpopulations of mesenchymal stem/stromal cells (MSCs) using single-cell RNA sequencing to elucidate the heterogeneity of the MSC population. MSCs present in mouse limb tissues could be classified into multiple groups. Additionally, we identified a cluster (Cluster 10) that exhibited acquisition of MSC gene patterns in response to stimulation. Using reporter mice that visualize genes specifically expressed in Cluster 10, we confirmed that Cluster 10 cells are localized at the ends of the femur bone. These Cluster 10 cells were found to be distributed in various parts of the mouse limbs and suggested to function as reservoir cells that are activated by growth or injury stimuli to supply mesenchymal cells.

Academic Significance and Societal Importance of the Research Achievements

間葉系幹細胞を用いた臨床応用が進んでいるが、細胞種類や性質の均一性が担保されておらず、治療効果の観点からのクオリティーコントロールの設定が急務である。申請者は細胞表面抗原を指標とした幹細胞特性解析を行ってきたが、治療効果の規格値設定は表面抗原マーカーのみでは不十分である。本研究では、申請者の技術と単一細胞の遺伝子発現を統合して解析することにより、幹細胞としての根本的な性質の理解を得る。組織幹細胞の詳細な知見を把握し、本国際共同研究を通して発信することは、国際的なコミュニティーの連携や密接なチームワークの創発の場となる。

Research Products

• [Int'l Joint Research] University of Cambridge(英国) (2020)
  • Year and Date: 2020-09-01
• [Journal Article] CD73-Positive Cell Spheroid Transplantation Attenuates Colonic Atrophy (2023)
  • 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
  • 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 Muscles (2023)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Hematopoietic-Mesenchymal Signals Regulate the Properties of Mesenchymal Stem Cells (2022)
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of activated microglia and macrophages by systemically administered DNA/RNA heteroduplex oligonucleotides (2022)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Novel Mesenchymal Stem Cell Spheroids with Enhanced Stem Cell Characteristics and Bone Regeneration Ability (2022)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] DNA/RNA heteroduplex oligonucleotide technology for regulating lymphocytes in vivo (2021)
  • Author(s): Ohyagi Masaki、Nagata Tetsuya、Ihara Kensuke、Yoshida-Tanaka Kie、Nishi Rieko、Miyata Haruka、Abe Aya、Mabuchi Yo、Akazawa Chihiro、Yokota Takanori
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 7344-7344
  • DOI: 10.1038/s41467-021-26902-8
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and Characterization of Tissue Resident CD29-Positive Progenitor Cells in Livestock to Generate a Three-Dimensional Meat Bud (2021)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cellular Heterogeneity of Mesenchymal Stem/Stromal Cells in the Bone Marrow (2021)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] A Shaking-Culture Method for Generating Bone Marrow Derived Mesenchymal Stromal/Stem Cell-Spheroids With Enhanced Multipotency in vitro (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Advantage of fat-derived CD73 positive cells from multiple human tissues, prospective isolated mesenchymal stromal cells (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] The extracellular domain of teneurin-4 promotes cell adhesion for oligodendrocyte differentiation (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Transcription factor Tlx1 marks a subset of lymphoid tissue organizer-like mesenchymal progenitor cells in the neonatal spleen (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Laminin α2, α4, and α5 Chains Positively Regulate Migration and Survival of Oligodendrocyte Precursor Cells (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids (2019)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sox9 regulates the luminal stem/progenitor cell properties of salivary glands (2019)
  • 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
  • Peer Reviewed / Open Access
• [Presentation] FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells (2020)
  • Author(s): YO MABUCHI
  • Organizer: 12th Stem Cell Society Singapore Symposium
  • 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
• [Book] Encyclopedia of Bone Biology. (2020)
  • Author(s): Mabuchi Yo
  • Total Pages: 7
  • Publisher: Elsevier Inc.
• [Book] Neural Crest Contributions to MSCs (2020)
  • Author(s): Yo Mabuchi
  • Total Pages: 7
  • Publisher: Reference Module in Biomedical Sciences
• [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/
• [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/
• [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/
• [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