Establishment of induced Pluriotent Stem cells with genomic stability by zygotic transcriptional factors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05100
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: YAMADA Mitsutoshi 慶應義塾大学, 医学部(信濃町), 講師 (40383864)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 胚性ゲノムの活性化 ZGA / iPS細胞 / 初期化 reprogramming / ゲノム安定性 / ES細胞 / 受精卵 / 生殖医学 / がん化

Outline of Final Research Achievements

Induced pluripotent stem cells (iPSCs)are expected to be useful for regenerative medicine such as drug screening and transplantation, which might particularly benefit older patients suffering from heart failure, diabetes and degenerative diseases. However, it is known that iPSCs isolated from aged somatic cells exhibit impaired genomic stability. In this study, we show that the Zygotic Genome Activation (ZGA) gene Zscan5b expressed from early embryonic development through the establishment process of embryonic stem cells (ESCs) and is involved in the genomic stability of ESCs. These results provide a new concept that loss of function of genes expressed in the early embryogenesis can lead to the loss of genomic stability of somatic and ES cells, resulting in random chromosomal aberrations. The findings would contribute to improve genomic stability of embryos and pluripotent stem cells, leading to the development of assisted reproduction technology and regenerative medicine.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、「受精後の初期に生じる遺伝子の機能を喪失させることで体細胞とESCsのゲノム安定性が損なわれ、ランダムに染色体異常が起こりえる」というあらたな概念を提示した。マウスモデルとヒトにおける遺伝子発現の時期は異なるため、本研究成果がそのままヒトに当てはまるかは今後さらなる検証が必要である。しかしながら今回の成果は、健全な受精卵の発育や幹細胞の樹立を通して、より安全な生殖補助医療および再生医療の実現に大きく寄与することが期待される。