Establishment of high efficient chromosomal aneuploidy rescue method by genome editing in iPS cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16520
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Akutsu Silvia Natsuko (AkutsuSilviaNatsuko) 広島大学, 原爆放射線医科学研究所, 助教 (10822299)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Trisomy rescue / iPSC / chromosome / cytogenetics

Outline of Final Research Achievements

I obtained dermal fibroblasts from eight patients with major human trisomy syndromes (trisomy 21, 18, 13, and 9 syndromes), established 190 clones of iPS cells, and comprehensively examined the copy number of genomic DNA in all clones. The number of copies of genomic DNA in all clones was detailed examined by karyotype, FISH, SNP and Sanger sequencing. As a result, the trisomy rescue phenomenon was confirmed in at least one cell line of each trisomy syndrome. Chromosome loss occurred regardless of parental origin. These results suggest that when pluripotency is induced by iPS cell reprogramming, 1) one of the trisomy chromosomes is randomly lost from the cells, and 2) cells normalized to disomy are sorted to form single iPS cell colonies. Furthermore, late lagging was postulated as the mechanism of chromosome loss.

Free Research Field

genetics

Academic Significance and Societal Importance of the Research Achievements

トリソミーレスキューは、着床前の初期胚でも観察されており、染色体数を正確に保つ生体のメカニズムの一つと考えられます。iPS細胞のトリソミーレスキューは、初期胚のトリソミーレスキューとメカニズムを共有する可能性があることから、本研究成果は生殖補助医療への貢献が期待されます。また、iPS細胞リプログラミングによるトリソミーレスキューは、ゲノム操作を伴わない染色体を修正する新たな治療法として、不妊症やがん治療などの再生・移植医療への応用が期待されます。