Functional analysis of miRNAs in spermatogonial stem cells
| Project/Area Number |
16K18556
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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 |
Developmental biology
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
Hirano Takamasa 国立遺伝学研究所, 遺伝形質研究系, 特任研究員 (30594999)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 生殖細胞 / P-body / 精子幹細胞 / 雄性生殖細胞 / NANOS2 / DND1 / 転写後制御 / 遺伝子転写後制御 / microRNA / 発生・分化 / 発現制御 / 遺伝学 / 細胞・組織 / 再生医学 |
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| Outline of Final Research Achievements |
In germ line cells, RNA-protein (RNP) granules are well developed. Spermatogonial stem cells (SSCs) have well-grown P-bodies, one of RNP granules. MicroRNA (miRNAs) pathway involves in P-body mediated mRNA regulation. I tried conditional disruption of miRNA biogenesis component (Dgcr8) in SSCs, but no obvious phenotypes. Next, I asked other P-body components, NANOS2 and DND1 proteins. NANOS2 and DND1 are germ cell specific RNA binding proteins and these proteins interact each other. Here, I reconstituted NANOS2-DND1 functions in somatic cell lines (N2D1 reconstituted cells). In germ cells, NANOS2-DND1 complex suppress mTORC1 activity and regulate cell growth. This mTOCR1 suppression and cell growth suppression was reproduced in N2D1 reconstituted cells. Furthermore, using N2D1 reconstituted cells I found 6 gene mRNAs as novel NANOS2-DND1 targets, suggesting that these six genes involved in SSC regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
NANOS2およびDND1は、精子幹細胞の維持だけでなく、始原生殖細胞の雄性分化にも関わることが知られている。しかし、これらの細胞は生体内で僅少であるため、標的となるmRNAの同定が遅れている。本研究では、生殖細胞特異的なNANOS2-DND1機能を体細胞で再構成することで、6種の標的候補遺伝子mRNAを同定した。今後、これら遺伝子の機能を明らかにすることで、生殖幹細胞維持や雄性分化の分子機構を明らかにすることが期待できる。さらに、微僅少な細胞でのみ発現するRNA結合タンパク質を体細胞で再構成することで、その分子機能に迫ることが可能であることを提唱した。
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Report
(4 results)
Research Products
(7 results)
