2022 Fiscal Year Final Research Report
Verification of the effect of De novo DNA methylation elimination on early embryogenesis of human ES/iPS cells.
| Project/Area Number |
20H03829
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | エピジェネティクス |
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| Outline of Final Research Achievements |
Human pluripotent stem cells (hPSCs) are in vitro products capable of differentiating into almost all the cells that make up the body. however, genome wide DNA methylation status of hPSCs are different compared to those of human preimplantation embryos (epiblast).
In this study, we asked how blocking of de novo DNA methyltransfereases activity in hPSCs affects transcriptome and epigenomic status. The deep sequencing analysis revealed that the effect of transcriptomic status in de novo DNA methyltransfereases deletion greatly depends on genetic background. Interestingly, we found that female cell specific abnormality, erosion of X-chromosome dosage compensation, is prevented by the mutations. Thus, our findings indicate that de novo DNA methyltransfereases activity is one of the drivers responsible for in vitro specific abnormality in hPSCs.
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| Free Research Field |
ヒト多能性幹細胞
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト多能性幹細胞は、体を構成するほぼ全ての細胞に分化可能な細胞であり、再生・細胞医療において中心的な役割を担っている。近年は、特定の疾患由来のiPS細胞など、疾患ゲノムを考慮したGenotype-Phenotype解析にも活用され、創薬開発分野でも注目を浴びている。
ヒト多能性幹細胞は、ヒトの初期胚細胞と同様の機能を持つと推測されているが、試験管産物特有の異常も報告されている。本研究では、ヒト多能性幹細胞の試験管産物特有の現象を解明することで、より高品質なヒト多能性幹細胞の作製と応用的基盤の構築を目指すことを目的とした。
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