| Project/Area Number |
13307028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | THE UNIVERSITY OF TOKYO (2002-2003)
University of Tsukuba (2001) |
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Principal Investigator |
NAKAUCHI Hiromitsu THE UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, PROFESSOR, 医科学研究所, 教授 (40175485)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMA Atsushi THE UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, LECTURER, 医科学研究所, 講師 (70244126)
EMA Hideo THE UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, ASSISTANT PROF., 医科学研究所, 助教授 (50344445)
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| Project Period (FY) |
2001 – 2003
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| Keywords | hematopoietic stem cells / self-renewal / plasticity |
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| Research Abstract |
Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate to multilineages. Clonal assay is therefore essential for their characterization. We have succeeded in a high degree of HSC purification and then established a clonal analysis for HSC potential after transplantation of one HSC into a mouse. Using this method, this study addressed two major issues regarding their plasticity and self-renewal limitation. We examined the distribution of HSC-derived cells in a variety of organs and tissues after transplantation of single HSCs isolated from GFP transgenic mice. GFP+ cells were widely distributed in various tissues, but most of them appeared to be positive for blood cell markers, and very few cells were considered to have non-hematopoietic phenotypes. These data suggest that HSCs have too little plasticity to contribute the regeneration of non-hematopoietic tissues. The clonal analysis of HSC self-renewal revealed that degrees to which they self-renew vary and that their self-renewal is extensive, but limited. It was further clarified that Bmi-1 belonging to Polycomb group genes is one of the molecules that restrict this capacity and that the signal adaptor protein, Lnk is strongly involved in events where HSCs decide to either self-renew or differentiate. Their precise mechanisms are under investigation.
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