| Project/Area Number |
15K08414
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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 |
Experimental pathology
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Ishikawa Naoshi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (30184485)
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| Research Collaborator |
Nakamura Ken-ichi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | テロメア / iPS細胞 / リプログラム / 染色体Q-FISH / 細胞老化 / 染色体特異性 / ヒト線維芽細胞 / リプログラミング / 線維芽細胞 |
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| Outline of Final Research Achievements |
To elucidate “lifelong” telomere dynamics at chromosomal level must contribute to clarify not only telomere biology but human aging process. We have analyzed sets of parental strains and derived iPSCs. Telomere lengths have been reported to be elongated in induced pluripotent stem cells (iPSC) during their reprograming process. However, the precise profiles of the telomere lengthen at chromosomal level have largely remain to be solved.
We analyzed telomere lengths by metaphase quantitative fluorescence in situ hybridization (Q-FISH) method, and found that the telomere lengths in iPSCs seem to be reflected neonatal state, and the telomere dynamics (lengthen or shorten) during the sequential subculture of human diploid fibroblast strains (TIG series) were different among each chromosome end. Frequencies of chromosomal instability (TAS) occurring differ among strains. The donor age of the cell strains was suggested to contribute the difference.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト正常２倍体細胞（線維芽細胞）の最初期から老化期に渡るテロメア長の “lifelong” プロファイルを明らかにすることはテロメア生物学に留まらず加齢科学の根幹の解明に資すると考えられる。
本研究では、ヒト線維芽細胞およびそれ由来のiPSCを染色体Q-FISH法により解析し、iPSCのテロメア長には細胞間および同一細胞内の染色体間でも大きな幅があるものの、iPS化に伴い由来細胞と比し平均値（中央値）は有意に増大し、リプログラムによってテロメア長伸長が起こることが確認出来た。以上の結果から、テロメア長はTERT活性亢進のみならずトリミング活性により染色体毎に巧妙に調節されることが示唆された。
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