2021 Fiscal Year Annual Research 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 | trisomy / rescue / iPSC |
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| Outline of Annual Research Achievements |
I successfully report the spontaneous correction from trisomy to disomy upon cell reprogramming in at least one cell line examined from trisomy syndromes (trisomy 21, 13, 18 and 9), and three possible combinations of chromosomes were selected in the isogenic trisomy-rescued iPSC clones. Single nucleotide polymorphism analysis showed that the trisomy-rescued clones exhibited either heterodisomy or segmental uniparental isodisomy, ruling out the possibility that two trisomic chromosomes were lost simultaneously and the remaining one was duplicated, suggesting instead that one trisomic chromosome was lost to generate disomic cells. These results demonstrated that trisomy rescue may be a phenomenon with random loss of the extra chromosome and subsequent selection for disomic iPSCs, which is analogous to the karyotype correction in early preimplantation embryos.
This results from this research was published in the online version of the American scientific journal "PLOS ONE" on March 11, 2022.
Trisomy rescue has also been observed in early embryos before implantation and is thought to be one of the biological mechanisms that maintain an accurate chromosome number. Since trisomy rescue of iPS cells may share a mechanism with trisomy rescue of early embryos, the results of this study are expected to contribute to assisted reproductive technology. In addition, trisomy rescue by iPS cell reprogramming is expected to be applied to regenerative medicine such as infertility and cancer treatment as a new therapeutic method for modifying chromosomes without genome manipulation.
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| Remarks |
2022/02/07, Excellent poster presentation,The 6th International Symposium of the Network-type Joint Usage/ Research Center for Radiation Disaster Medical Science
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[Presentation] トリソミー症候群の細胞初期化で誘導されるトリソミーレスキュー2021
Author(s)
Silvia Natsuko Akutsu, Tatsuo Miyamoto, Keita Tomioka, Daiju Oba, Hirofumi Ohashi, Shinya Matsuura
Organizer
The 5th International Symposium of the Network-type Joint Usage/ Research Center for Radiation Disaster Medicine Science
Int'l Joint Research
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