2017 Fiscal Year Final Research Report
Mechanism of the maintenance of hematopoietic and leukemia stem cells by deubiquitinating enzyme USP10
| Project/Area Number |
15K09469
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kanazawa Medical University (2016-2017)
Niigata University (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | USP10 / 造血肝細胞 / 脱ユビキチン化酵素 / アポトーシス |
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| Outline of Final Research Achievements |
Ubiquitin specific peptidase 10 (USP10) is involved in cellular stress responses and we made USP10 knockout (KO) mice to analyze its in vivo functions. All USP10 KO mice died within 1 year after birth because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of hematopoieic stem cells (HCSs) in bone marrow and fetal liver. Such USP10-KO fetal liver started to exhibit enhanced apoptosis of HSCs at around E14.5. Transplantation of USP10 KO HSCs into irradiated WT mice failed to reconstitute multilineage hematopoiesis, whereas transplantation of USP10-competent bone marrow cells into USP10-KO mice did. These results suggest that USP10 is an essential deubiquitinase for hematopoiesis and functions by inhibiting apoptosis of HSCs.
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| Free Research Field |
血液学 ウイルス学 細胞生物学
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