Elucidation of super-undifferentiated state of mouse ES cells and application to reprogramming of ES/iPS cells of other species

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04683
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nara Medical University
• Principal Investigator: Horie Kyoji 奈良県立医科大学, 医学部, 教授 (30333446)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ES細胞 / iPS細胞 / 遺伝子 / 未分化状態 / 分化 / CRISPR

Outline of Final Research Achievements

We identified a novel heterogeneity in mouse ES cells. By comprehensive analysis of gene expression, we identified a highly undifferentiated cell population. We also showed that chimeric mice could be produced from this cell population with high efficiency, demonstrating the high pluripotency of this cell population. Furthermore, the transcription factor network that regulates this heterogeneity was identified by measuring the transcription factor activity at the one-cell level and by disrupting transcription factors using CRISPR/Cas9. The manipulation of this network may lead to producing high-quality ES/iPS cells in species other than mice.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、マウスES細胞の解析を通じて、一見して均一に見えるマウスES細胞の多能性が、個々の細胞ごとに異なることを明らかにした。さらに、多能性状態の不均一性を制御する遺伝子群を同定し、これらの遺伝子群の発現レベルを変えることで、多能性状態を人為的に操作できる可能性を示した。この遺伝子群は、ヒトをはじめとする他の生物種でも保存されている。よって、今回の知見は、様々な生物種のES/iPS細胞へも適用できると考えられ、再生医学や発生生物学の発展への寄与を期待できる。