Induction of self-renewal in single hematopoietic stem cells

• Project/Area Number: 25293221
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kumamoto University (2016); Keio University (2013-2015)
• Principal Investigator: Ema Hideo 熊本大学, 国際先端医学研究機構, 教授 (50344445)
• Co-Investigator(Kenkyū-buntansha): 滝澤 仁 熊本大学, 国際先端医学研究機構, 特別招聘准教授 (10630866)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 血液内科 / 血液内科学 / 造血幹細胞

Outline of Final Research Achievements

We previously showed that multiple cytokines can directly stimulate long-term hematopoietic stem cells (LT-HSC), resulting in their self-renewal. However, whether different cytokines lead to the expansion of different types of HSC was not known. In this study, we focused on thrombopoietin (TPO) and interleukin-12 (IL-12), and compared their self-renewal-inducing effects using single-cell culture combined with transplantation assay. Data showed that the number of short term-HSC was significantly increased after the culture with stem cells factor (SCF)+TPO or SCF+IL-12. Data also suggested that some LT-HSCs were expanded after those cultures. On-going experiments will confirm these findings and also clarify their different effects.

Research Products

• [Journal Article] Repopulation dynamics of single hematopoietic stem cells in mouse transplantation experiments: importance of stem cell composition in competitor cells (2016)
  • Author(s): Ema, H., Uchinomiya, K., Morita, Y., Suda, T., & Iwasa, Y.
  • Journal Title: Journal of Theoretical Biology Volume: 394 Pages: 57-67
  • DOI: 10.1016/j.jtbi.2016.01.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mechanisms of self-renewal in hematopoietic stem cells (2016)
  • Author(s): Wang Z, Ema H
  • Journal Title: Int J Hematol Volume: 103 Issue: 5 Pages: 498-509
  • DOI: 10.1007/s12185-015-1919-5
  • Peer Reviewed
• [Journal Article] Heterogeneity and hierarchy of hematopoietic stem cells (2014)
  • Author(s): Ema H, Morita Y, and Suda T
  • Journal Title: Exp Hematol Volume: 42 Pages: 74-82
  • Peer Reviewed
• [Journal Article] Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells (2013)
  • Author(s): Yamamoto R et al.
  • Journal Title: Cell Volume: 154 Pages: 1112-26
  • Peer Reviewed
• [Journal Article] Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method (2013)
  • Author(s): Hamanaka S et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 435 Pages: 586-91
  • Peer Reviewed
• [Presentation] Early and late leukemic stem cells in murine leukemia models (2016)
  • Author(s): Dong F, Bai H, Zhang S, Wang X, Wang J, Wang Z, Xie M, Hao S, Cheng T, Ema H
  • Organizer: 58th Americal Society of Hematology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] The origins of gene mutations and leukemic stemc ells in mouse acute leukemia models (2016)
  • Author(s): Ema H, Wang X, Dong F
  • Organizer: 5th International Forum on Stem ells
  • Place of Presentation: Tianjin, China
  • Year and Date: 2016-10-28
  • Int'l Joint Research / Invited
• [Presentation] A new view of differentiation pathways from hematopoietic stem cells (2014)
  • Author(s): Ema H
  • Organizer: International Forum on Stem Cell
  • Place of Presentation: Tianjin, China
  • Year and Date: 2014-11-01 – 2014-11-03
  • Invited
• [Presentation] Distinction among long-term HSCs, short-term HSCs, and repopulating CMPs by a novel in vitro single-cell assay (2014)
  • Author(s): Ema H, O'Neill A, Suda T
  • Organizer: International Society of Experimental Hematology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-08-21 – 2014-08-24
• [Presentation] In vitro G0 phase assay for hematopoietic stem cells (2013)
  • Author(s): O'Neill A, Suda T, and Ema H
  • Organizer: 日本血液学会
  • Place of Presentation: 札幌