Single cell transcriptome analysis on circulating mesenchymal stem cells during tissue regeneration

• Project/Area Number: 18K16027
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Osaka University
• Principal Investigator: Shimbo Takashi 大阪大学, 医学系研究科, 寄附講座准教授 (70780609)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シングルセルRNA-seq / 表皮水疱症 / 間葉系幹細胞 / 再生医療 / 骨髄由来PDGFRα陽性間葉系幹細胞 / 単一細胞網羅的遺伝子発現解析 / 組織再生 / single cell / rna-seq

Outline of Final Research Achievements

The supply of cells to damaged tissue is essential for functional tissue regeneration. Using a mouse model of epidermolysis bullosa, we found that the supply of bone marrow-derived PDGFRα-positive mesenchymal stem cells is important for tissue regeneration. In this project, we comprehensively identified functional subpopulations in circulating bone marrow-derived PDGFRα-positive mesenchymal stem cells involved in tissue regeneration by single-cell RNA-seq analysis. We successfully identified functional subpopulations in the bone marrow-derived PDGFRα-positive mesenchymal stem cell pool. We also demonstrated that bone marrow-derived PDGFRα-positive mesenchymal stem cells can differentiate and exert diverse functions in the mobilized damaged tissues.

Academic Significance and Societal Importance of the Research Achievements

間葉系幹細胞の高い抗炎症作用や分化能は、再生医療の分野で注目を集め内外で積極的に研究されている。我々が着目する生体に元来備わっている組織再生メカニズムを促進する組織再生誘導機構では、体外での幹細胞培養が不要であるため癌化のリスクはなく表皮水疱症新規治療法として有望である。組織再生誘導を担う末梢循環骨髄由来PDGFRα陽性間葉系幹細胞を単一細胞レベルで網羅的に解析し、その組織修復メカニズムを明らかにしようと試みる本研究は先駆的かつ革新的である。また末梢循環間葉系幹細胞には未解明な点が多く、生物学、発生学、幹細胞学の観点からも学術的価値は非常に高いと考える。

Research Products

• [Journal Article] Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus (2019)
  • Author(s): Shimbo, T., Endo, M., Iwai; S., Kitayama, T., Ouchi, Y., Yamamoto, R., Takaki, E., Yamazaki, S., Nishida, M., Wang, X., Kikuchi, Y., Tomimatsu, T., Kaneda, Y., Kimura, T. Tamai, K
  • Journal Title: Biochemical and Biophysical Research Communications Volume: pii: S0006-291X(19) Issue: 2 Pages: 30410-3
  • DOI: 10.1016/j.bbrc.2019.03.033
  • Peer Reviewed / Open Access
• [Presentation] Single cell RNA-seq and single cell ATAC-seq analyses during a treatment for dystrophic epidermolysis bullosa (2019)
  • Author(s): Takashi Shimbo, Sho Yamazaki, Tomomi Kitayama, Yuya Ouchi, Ryoma Yamamoto, Eiichi Takaki, Leena Bruckner- Tuderman, Jouni Uitto, Yasufumi Kaneda, Katsuto Tamai
  • Organizer: Society for Investigative Dermatology 77th
  • Int'l Joint Research
• [Presentation] TRANSCRIPTOME AND EPIGENOME ANALYSES FOR REGENERATED SKIN IN A RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA MOUSE MODEL (2019)
  • Author(s): Takashi Shimbo, Sho Yamazaki, Tomomi Kitayama, Yuya Ouchi, Ryoma Yamamoto, Eiichi Takaki, Leena Bruckner- Tuderman, Jouni Uitto, Yasufumi Kaneda, Katsuto Tamai
  • Organizer: International Society for Stem Cell Research
  • Int'l Joint Research
• [Presentation] 網羅的単一細胞遺伝子発現解析が明らかにしたマウス潰瘍性大腸炎増悪メカニズム (2019)
  • Author(s): 新保敬史、Ho Yen-Ting、北山智美、大内雄矢、Edward Wijaya、金田安史、玉井克人
  • Organizer: 第40回日本炎症・再生医学会
• [Presentation] Single cell transcriptome and epigenome analyses in a murine model of dystrophic epidermolysis bullosa (2019)
  • Author(s): Takashi Shimbo, Sho Yamazaki, Tomomi Kitayama, Yuya Ouchi, Ryoma Yamamoto, Eiichi Takaki, Leena Bruckner- Tuderman, Jouni Uitto, Yasufumi Kaneda, Katsuto Tamai
  • Organizer: The 49th European Society for Dermatology
  • Int'l Joint Research
• [Presentation] Single cell RNA- and ATAC-seq analyses in a murine model of dystrophic epidermolysis bullosa (2019)
  • Author(s): Takashi Shimbo, Sho Yamazaki, Tomomi Kitayama, Yuya Ouchi, Ryoma Yamamoto, Eiichi Takaki,Leena Bruckner-Tuderman, Jouni Uitto, Yasufumi Kaneda, Katsuto Tamai
  • Organizer: 第44回日本研究皮膚科学会