Identification of activated hematopoietic stem cell niche using in vivo imaging technology

• Project/Area Number: 15H06373
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: SUDO Takao 大阪大学, 生命機能研究科, 助教 (80631184)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 造血幹細胞 / 造血幹細胞ニッチ / 細胞周期 / 生体イメージング / RNA-Seq法 / 活性化マーカー

Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) maintain the turnover of mature blood cells in bone marrow (BM). The cell-cycle status of HSCs are known to fluctuate according to physiological circumstances. However, precise mechanisms regulating HSCs status remain elusive.We performed dynamic live imaging of BM to analyze homeostatic or activated HSCs using multiphoton microscopy. The mean velocity and displacement of HSCs transplanted into 5-fluorouracil (5-FU) treated mice were significantly decreased compared to those transplanted into control mice. Moreover, most of transplanted HSCs in 5-FU treated recipients were adjacent to endothelial cells. Gene expression analyses revealed that expression levels of cell-cycle related genes in transplanted cells were different between these 2 recipient groups. These results suggested that microenvironments after BM injury supply proliferative signals to HSCs and influence cell-cycle status of them.

Research Products

• [Journal Article] Endothelial cell-selective adhesion molecule expression in hematopoietic stem/progenitor cells is essential for erythropoiesis recovery after bone marrow injury. (2016)
  • Author(s): Sudo T, Yokota T, Okuzaki D, Ueda T, Ichii M, Ishibashi T, Isono T, Habuchi Y, Oritani K, Kanakura Y.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0154189-e0154189
  • DOI: 10.1371/journal.pone.0154189
  • Peer Reviewed / Open Access
• [Journal Article] ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias. (2016)
  • Author(s): Ishibashi T, Yokota T, Tanaka H, Ichii M, Sudo T, Satoh Y, Doi Y, Ueda T, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Journal Title: Experimental Hematology Volume: 44 Issue: 4 Pages: 269-281
  • DOI: 10.1016/j.exphem.2015.12.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Estrogen-inducible sFRP5 inhibits early B-lymphopoiesis in vivo, but not during pregnancy (2015)
  • Author(s): Takafumi Yokota, Kenji Oritani, Takao Sudo, Tomohiko Ishibashi1, Yukiko Doi, Yoko Habuchi, Michiko Ichii, Kentaro Fukushima, Daisuke Okuzaki, Kazuma Tomizuka, Kengo Yamawaki, Makoto Kakitani, Akihiko Shimono, Eiichi Morii, Paul W. Kincade, Yuzuru Kanakura
  • Journal Title: European Journal of Immunology Volume: in press Issue: 5 Pages: 1390-1401
  • DOI: 10.1002/eji.201444939
  • Peer Reviewed / Open Access
• [Journal Article] Role of endothelial antigen ESAM in activated hematopoietic stem cells (2015)
  • Author(s): Sudo T, Yokota T, Kanakura Y
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 5 Pages: 464-474
  • DOI: 10.11406/rinketsu.56.464
  • NAID: 130005076019
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Presentation] Dynamic analysis of activated hematopoietic stem and progenitor cells in bone marrow (2016)
  • Author(s): Sudo T, Mizuno H, Ishii M
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-13