2019 Fiscal Year Research-status Report
Establishment of high efficient chromosomal aneuploidy rescue method by genome editing in iPS cells
| Project/Area Number |
19K16520
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| Research Institution | Hiroshima University |
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Principal Investigator |
阿久津 シルビア夏子 (AkutsuSilviaNatsuko) 広島大学, 原爆放射線医科学研究所, 助教 (10822299)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | iPS cells / Chromosome / Aneuploidy / Reprogramming / Down syndrome |
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| Outline of Annual Research Achievements |
Down's syndrome is the most prevalent chromosomal aneuploidy caused by trisomy 21, but its curative cure has not yet been established. Recently, the possibility of a "chromosomal aneuploidy therapy" in which trisomy 21 is rescued was demonstrated by reprogramming iPS cells. Here, I proposed to reproduce this approach and increase the aneuploidy rescue efficiency that was shown as extremely low, being a major obstacle for future basic research and clinical application of aneuploidy rescue. Currently, I am establishing a highly efficient chromosomal aneuploidy rescue experimental protocol for trisomy disorders.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The highly efficient chromosomal aneuploidy rescue experimental protocol is being established for trisomy 21 and another trisomy disorders. Successfully, primary fibroblasts from trisomy disorders showed karyotype rescue after reprogramming to iPS cells. The Fluorescence In situ Hybridization (FISH) and karyotype analysis were performed to confirm the results. The reproducibility results from previous studies have been successfully obtained. The results of this research will be an epoch-making basic technology for the root cure of aneuploidy diseases.
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| Strategy for Future Research Activity |
The next step in the research is to test protocols for rescuing aneuploidies in different cell lines of the same aneuploidy diseases. When the protocol is well established, it will be possible to begin the investigation of the trisomy rescue mechanism during cellular reprogramming.
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| Causes of Carryover |
The next fiscal year, I plan to construct a new detection system targeting different fluorescent dye-expressing genes on chromosome 21 of Down syndrome iPSCs by genome editing to evaluate the rescue of trisomy in the reprogramming process. The results will be presented in the Annual Meeting Society of Genetics.
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