Mechanisms of expansion of hematopoietic stem cell clones

• Project/Area Number: 25670447
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: HIRAO Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350)
• Co-Investigator(Kenkyū-buntansha): TADOKORO Yuko 金沢大学, がん進展制御研究所, 助教 (00447343)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 造血幹細胞 / 幹細胞クローン

Outline of Final Research Achievements

It has been shown that quality of individual hematopoietic stem cells are highly variable. In this study, we analyzed functions of molecules in Ras signals in hematopoetic stem cell competition during hematopoietic reconstitution. We found that Spred1, a negative regulator of Ras/Raf/Erk, plays a critical role in dominancy of hematopoietic stem cells in a competitive assay in vivo. Further studies of Spred1-mediated control of self-renewal activity of hematopoietic stem cells would lead to deep understanding of stem cell aging and tumorigenesis.

Research Products

• [Journal Article] Pleiotropic roles of mTOR complexes in haemato-lymphopoiesis and leukemogenesis. (2014)
  • Author(s): Hoshii T, Matsuda S, Hirao A.
  • Journal Title: J Biochem. Volume: 156 Issue: 2 Pages: 73-83
  • DOI: 10.1093/jb/mvu037
  • NAID: 40020155036
  • Peer Reviewed
• [Journal Article] Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells. (2013)
  • Author(s): Hoshii T, Kasada A, Hatakeyama T, Ohtani M, Tadokoro Y, Naka K, Ikenoue T, Ikawa T, Kawamoto H, Fehling HJ, Araki K, Yamamura K, Matsuda S, Hirao A
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 10 Pages: 3805-3810
  • DOI: 10.1073/pnas.1320265111
  • Peer Reviewed
• [Presentation] Role of c-Kit signal modulation in the control of self-renewal and aging of hematopoietic stem cells. (2015)
  • Author(s): Hirao A
  • Organizer: 2015 US-Japan meeting on malignant hematopoiesis and stem cells.
  • Place of Presentation: 米国
  • Year and Date: 2015-03-16 – 2015-03-17
  • Invited
• [Presentation] The signaling pathways for the determination of hematopoietic stem cell fate. (2014)
  • Author(s): 平尾 敦
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] The nutrient sensing signaling pathways in the hematopoietic stem cells and leukemia. (2013)
  • Author(s): Hirao A
  • Organizer: SUCRI-KUCRI Joint Symposium
  • Place of Presentation: Seoul National University (Korea)
  • Invited
• [Presentation] The nutrient sensing signaling pathways in the hematopoietic stem cells and leukemia. (2013)
  • Author(s): Hirao A
  • Organizer: The 23th Hot Spring Harbor International Symposium
  • Place of Presentation: Kyushu University(Fukuoka)
  • Invited
• [Presentation] 栄養センサーシグナルと幹細胞制御 (2013)
  • Author(s): 平尾敦
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Invited