| Project/Area Number |
16KT0113
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund |
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| Section | 特設分野 |
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| Research Field |
Complex Systems Disease Theory
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| Research Institution | Kumamoto University |
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Principal Investigator |
Sashida Goro 熊本大学, 国際先端医学研究機構, 特別招聘教授 (70349447)
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| Co-Investigator(Kenkyū-buntansha) |
松井 啓隆 熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
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| Project Period (FY) |
2016-07-19 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 骨髄異形成症候群 / 老化 / 造血幹細胞 / クローン造血 / 環境ストレス / DNAメチル化 / ヒストン修飾 / エピゲノム / ストレス / 感染 |
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| Outline of Final Research Achievements |
Myelodysplastic syndrome, which is more common in the elderly, is a clonal hematopoietic tumor that occurs from hematopoietic stem cells. In order to understand the functional decline of tissue stem cells due to environmental stress over life and the disease onset mechanism, we developed genetic analysis and verification using a mouse biological model in conjunction with analysis using clinical specimens. In this study, the analysis using existing gene expression data also strongly suggested the enhancement of inflammatory stress signal and the involvement in MDS disease state. Based on these findings, in order to prevent the onset of MDS, we have inhibited infection-stress signals as well as remodeled an epigenomic state of MDS stem cells into that of normal hematopoietic stem cells.
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| Academic Significance and Societal Importance of the Research Achievements |
老化による複雑な生物学的応答のもとで、臓器の機能低下やがんを含めた疾患を発症させる機序は明白でない。高齢者に好発する骨髄異形成症候群は造血幹細胞より発生するクローン性造血器腫瘍であり、生涯に渉った環境ストレスによるがん発症の仕組みは不明であった。本研究課題では、MDS幹細胞の遺伝子発現解析データなどの統合的検証によってMDS発症の責任因子を絞り込むとともに、申請者が新たに作製したMDS発症モデルマウスを用いて、MDS発症機序の分子基盤解明を試みた。今後のさらなる研究の展開を図っている。
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