Genome Maintenance Mechanisms in Pluropotent Stem Cells
| Project/Area Number |
16K07382
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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 |
Developmental biology
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| Research Institution | National Institute for Basic Biology |
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Principal Investigator |
Tsubouchi Tomomi 基礎生物学研究所, 幹細胞生物学研究室, 准教授 (70754505)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 胚性幹細胞 / ゲノム恒常性 / DNA複製 / dNTP / ES細胞 / dNTP産生 / DNA 複製 / ｄNTP産生 / 幹細胞 |
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| Outline of Final Research Achievements |
Embryonic stem cells are the stem cells that are established from an early stage of a developing embryo. ES cells are the origin of cell types of several hundreds that compose our bodies, and they are known to hold properties that are unique in various aspects of cell division cycle. During this research period, we found that replication machinery progress slowly at all stage of DNA replication (S) phase, and found that this is due to reduced amount of dNTPs. Despite the slow replication-machinery, ES cells complete DNA synthesis within similar amount of time compared to MEFs. Our results show that this is due to denser distribution of active DNA replication machinery along the genome.
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| Academic Significance and Societal Importance of the Research Achievements |
ES細胞を含む多能性幹細胞は、体を構成する数百種類の細胞種を生み出す能力を持ち、再生医療への応用が期待されている。しかしながら生物体内では個体発生のごく初期に短期間にのみ存在する細胞群であり、ES細胞そのものの理解は不完全である。本研究ではES細胞のDNA複製制御に着目し、1) ES細胞が特有のDNA複製制御を持ち、ゲノム全体のDNA複製が時間内に確実に終了するよう制御されていること 2) ES細胞特異的なDNA複製制御には細胞内で合成されるdNTP量が他の細胞種と比較して低く維持されていること を明らかにした。本研究よりES細胞の維持にdNTP量が重要なファクターであることが明らかになった。
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Report
(4 results)
Research Products
(12 results)
