Megakaryocytes determine the cell fate of hematopoietic stem cells

• Project/Area Number: 26713035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Hematology
• Research Institution: Kumamoto University
• Principal Investigator: Nakamura-Ishizu Ayako 熊本大学, 国際先端医学研究機構, 客員准教授 (10548548)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 造血幹細胞 / 巨核球 / 分化 / ニッチ / ポドプラニン / CLEC2

Outline of Final Research Achievements

The maintenance, proliferation and differentiation of hematopoietic stem cell (HSC) within the bone marrow (BM) microenvironment is essential for healthy hematopoiesis. in this project we have investigated the role of mature megakaryocytes in regulating hematopoietic stem cells in the BM. Wh have characterized CLEC2 expressing Megakaryocvtes as potent niche cells and have reported their function in maintaining HSCs in quiescence. We are further preparing to report the effect of CLEC2 receptor podoplanin in BM hematopoiesis and the role of the cytokine, Thrombopoietin in determining HSC cell fate.

Research Products

• [Int'l Joint Research] シンガポール国立大学(シンガポール)
• [Journal Article] CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow. (2015)
  • Author(s): Nakamura-Ishizu A, Takubo K, Kobayashi H, Suzuki-Inoue K, Suda T.
  • Journal Title: J Exp Med. Volume: 212 Issue: 12 Pages: 2133-46
  • DOI: 10.1084/jem.20150057
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin (2014)
  • Author(s): Nakamura-Ishizu A, Takubo K, Fujioka M, Suda T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 454(2) Issue: 2 Pages: 353-7
  • DOI: 10.1016/j.bbrc.2014.10.095
  • Peer Reviewed / Open Access
• [Journal Article] The analysis, roles and regulation of quiescence in hematopoietic stem cells (2014)
  • Author(s): Nakamura-Ishizu A, Takizawa H, Suda T.
  • Journal Title: Development Volume: 141(24) Issue: 24 Pages: 4656-66
  • DOI: 10.1242/dev.106575
  • Peer Reviewed / Open Access
• [Journal Article] Aging of the hematopoietic stem cell niche (2014)
  • Author(s): Ayako Nakamura-Ishizu, Toshio Suda
  • Journal Title: Int J Hematol Volume: 100(4): Issue: 4 Pages: 317-25
  • DOI: 10.1007/s12185-014-1641-8
  • Open Access
• [Presentation] Thrombopoietin mediates metabolic priming of hematopoietic stem cells for rapid megakaryocyte lineage differentiation (2018)
  • Author(s): Ayako Ishizu
  • Organizer: Stem cell symposium
  • Invited
• [Presentation] Thrombopoietin-mediated exit from quiescence involves metabolic priming of hematopoietic stem cells for rapid megakaryocyte lineage differentiation (2017)
  • Author(s): Ayako Ishizu
  • Organizer: ISEH
  • Int'l Joint Research
• [Presentation] Rapid and direct megakaryocyte-lineage differentiation from HSCs hallmark hematopoietic system response to stress (2016)
  • Author(s): Ayako Ishizu
  • Organizer: ISEH
  • Place of Presentation: San Diego
  • Year and Date: 2016-08-25
  • Int'l Joint Research
• [Presentation] CLEC-2 signaling is crucial for the production of thrombopoietin in the megakaryocyte niche (2015)
  • Author(s): Ayako Nakamura-Ishizu
  • Organizer: ISEH
  • Place of Presentation: Kyoto 京都国際会議場
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] 血小板活性化型受容体CLEC-2 を介した造血幹細胞と骨髄血管ニッチの相互制御 (2015)
  • Author(s): 石津 綾子
  • Organizer: 日本解剖学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited