| 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)
中村 幸夫 筑波大学, 基礎医学系, 講師 (60231479)
渋谷 彰 筑波大学, 基礎医学系, 助教授 (80216027)
小野寺 雅史 筑波大学, 臨床医学系, 講師 (10334062)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥53,950,000 (Direct Cost: ¥41,500,000、Indirect Cost: ¥12,450,000)
Fiscal Year 2003: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2002: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2001: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
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| Keywords | hematopoietic stem cells / self-renewal / plasticity / 造血肝細胞 / 血管内皮前駆細胞 / lnk / アダプター分子 / Gfi-1B / 肝幹細胞 / 自己複製能 / SP細胞 / ABC transporter / bcrp-1 / ABCG2 |
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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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