2005 Fiscal Year Final Research Report Summary
Molecular mechanisms making the difference between leukemic stem cells and hematopoietic stem cells
| Project/Area Number |
16590921
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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 | Tohoku University |
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Principal Investigator |
MINEGISHI Naoko Tohoku University, Biomedical Engineering Research Organization, Associate Professor, 先進医工学研究機構, 助教授 (40271895)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hematopoietic stem cells / transcription factor / proteasome / ubiquitin / cell cycle / leukemia |
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| Research Abstract |
Leukemic stem cells, a small fraction of leukemic cells with the capacity to cause leukemia in transplanted animals, have the characteristics very similar to those of hematopoietic stem cells. The hematopoietic stem cells are the good candidates for the cell therapy and the regenerative medicine. Therefore, it is an urgent issue to elucidate the differences between the two types of stem cells, in order to handle normal stem cells ex vivo without the fear of the therapy-induced malignancies, and to find the new targets of leukemia therapies.
We have studied on the transcription factor GATA2, an indispensable factor for the proliferation and survival of the hematopoietic stem cells. Under the support of the scientific research fund, we first found the short half-life of the GATA2 protein and the contribition of the protein degradation pathway on the rapid control of GATA2 expression (1). Secondly, We carried out the transgenic mice reporter analysis, and revealed the regulatory domain driving the GATA2 gene transcription in the hematopoietic cells of murine embryos (2). This regulatory domain was only active in vivo, and had the indispensable GATA-factor binding sequences, suggesting the positive feedback regulation of GATA2 expression. Thirdly, we analyzed the green fluorescent protein (GFP) expression in the hematopoietic stem cell fraction of the mice having the genetic insertion of GFP cDNA into the transcriptional start site of GATA2 gene, and demonstrated the expression of the GFP/GATA2 and Sca1 in the long-term reconstituting hematopoietic stem cells (3,). The video imaging of the living bone marrows of these mice revealed the active "niche" structures, the previously conceptual microenvironments nursing hematopoietic stem cells. Hematopoietic stem cells attached to the osteoblasts, and seemed to receive the signals from the osteoblasts.
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