2005 Fiscal Year Final Research Report Summary
Molecular mechanisms for regulation of hematopoietic stem cells and leukemic stem cells
| Project/Area Number |
16590964
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kanazawa University (2005)
Keio University (2004) |
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Principal Investigator |
HIRAO Atsushi Kanazawa University, Division of Molecular Genetics, Cancer Research Institute, professor, がん研究所, 教授 (90343350)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hematopoietic stem cell / leukemia |
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| Research Abstract |
We demonstrated that side population (SP), based on FACS analysis with Hoechst33342, in c-kit+Sca-1+Lin-(KSL) cells represents a population of quiescent hematopoietic stem cells (HSCs). Cell cycle analysis with BrdU labeling showed that SP were slowly cycling in GO phase. HSCs mobilized in peripheral blood from a bone marrow niche by G-CSF or 5-FU treatment were cycling and those cycling HSCs were not in SP.HSCs in developing mice, which were cycling and expanding, were also in main population (MP). SP cells in KSL fraction were resistant to myelosuppressive stress including X-ray and 5-FU treatment which depletes cycling hematopoietic cells. Histological examination revealed that the 5-FU resistant HSCs were surrounded by bone-lining osteoblast-like cells on the surface of the bone. These data indicate that the osteoblastic zone is a niche for quiescent HSCs in bone marrow. Recently tumorigenic or tumor-initiating cells, which are called cancer stem cells, have been identified. We attempted to identify cancer stem cells by using SP fraction. We established leukemia model by retroviral infection carrying HoxA9 and Meis1. The leukemia cells included SP cells in bone marrow. However transplantation experiments did not showed the evidence showing that leukemic stem cells were enriched in SP fraction. These data suggest requirement of another markers for identification of cancer stem cells.
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Research Products
(10 results)
