| Project/Area Number |
17K16191
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 造血幹細胞 / オートファジー / ミトコンドリア |
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| Outline of Final Research Achievements |
Several studies have shown that cell fate of HSCs is dependent on mitochondrial quality and function, which might be controlled by autophagy process. In this study, we clarified how deficiency of autophagy-related gene 7(Atg7) induce hematopoietic failure.
At first, we analyzed mitochondria status (membrane potential=ΔΨm, mitochondrial ROS production) in Atg7KO mice HSCs in each age. We found that ΔΨm and ROS production is no difference between neonatal stage but it will show difference from 4-weeks old mice. Actually, quiescent HSCs are seen after 4-weeks old in WT, while Atg7KO HSCs fail to enter quiescence. Furthermore, total bone marrow cell number and frequency of HSCs significantly decreased in Atg7KO mice with growing. Finally, we performed neonatal BMCs competitive transplantation assay, and found no defective reconstitution of Atg7KO BMCs. Here we concluded that autophagy process is involved in the maintaining quiescence in adult HSCs but not in neonatal HSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
臍帯血由来の造血幹細胞は回収できる数は少ないが造血幹細胞としての質、機能は成人から回収したものに比べ良い状態を示す。しかし、成人患者への移植には多数の造血幹細胞が必要であり臍帯血からの造血幹細胞では不十分である。しかし、幼児期造血幹細胞の性質を解明することで成人造血幹細胞の機能を幼児期型に近づけることができれば、質の良い造血幹細胞を患者に提供することが可能となる。本研究で明らかにしたオートファジーは幼児期造血幹細胞維持には関連しないと言った知見は今後のex vivoでの幼児期造血幹細胞増殖、成人造血幹細胞を幼児期様造血幹細胞に近づけ移植する方法の開発に貢献できるものと考える。
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