| Project/Area Number |
25290068
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Genome biology
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
ARAKI RYOKO 国立研究開発法人放射線医学総合研究所, 研究基盤センター, 室長 (40392211)
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| Co-Investigator(Renkei-kenkyūsha) |
FUJIMORI YUKO (HOKI YUKO) 放射線医学総合研究所, 研究基盤センター・研究基盤技術部, 研究員 (50415402)
SUNAYAMA MISATO 放射線医学総合研究所, 研究基盤センター・研究基盤技術部, 技術員 (20625115)
SUGIURA MAYUMI 放射線医学総合研究所, 研究基盤センター・研究基盤技術部, 主任研究員 (60397841)
UDA MASAHIRO 放射線医学総合研究所, 研究基盤センター・研究基盤技術部, 技術員 (30625893)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | リプログラミング / iPS細胞 / 点突然変異 / ES細胞 |
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| Outline of Final Research Achievements |
A significant number of point mutations have been suggested in all iPSC genomes examined thus far, arousing serious concerns about the use of iPSCs especially on immunogenicity and tumorigenesis. Here, we have developed a genome sequencing system which allows us to exclusively identify de novo point mutations and have attempted to reveal the amount and mode of point mutations. First, we compared iPSCs with ESCs and found more than 10 times point mutations in iPSC genomes compared to those in ESC genomes. Further, the point mutations observed in iPSC genomes exhibit a unique base substitution pattern, transversion-predominant. Next, we focused on the heterogeneity in an iPSC clone to directly identify the point mutations that arose during the iPSC generation. As a result, we found a large number of SNVs (single nucleotide variations), of which allele frequency were less than 50%. Our results indicates that current iPSC generation method contains mutagenic process.
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