Analyses on developmental transition process of mammalian pluripotent cells and its epigenomic regulations using single cell technologies

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02424
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: ABE KUNIYA 国立研究開発法人理化学研究所, バイオリソース研究センター, チームリーダー (40240915)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 細胞分化 / 分化遷移 / 多能性幹細胞 / Ｘ染色体不活性化 / シングルセル解析

Outline of Final Research Achievements

Single-cell RNA-Seq analysis of naive-primed transition process was performed and 3 clusters that exhibit characteristics other than ES cells and EpiSC were identified. We estimated the time of appearance of each cluster after induction of differentiation by pseudotime analysis, and extracted a group of genes with high expression specificity to each cluster. One of the newly identified clusters had a morphology similar to that of EpiSCs but with a different expression profile, suggesting that it was a novel pluripotent stem cell. Interestingly, another cluster showed a genome-wide downregulation of gene expression, and it appears that X chromosome inactivation initiates in this cluster.

Free Research Field

発生遺伝学、幹細胞学、ゲノム科学

Academic Significance and Societal Importance of the Research Achievements

細胞分化の進行を考える時、1）時間の経過と伴に徐々に、しかし確実に細胞形質が漸進的に変化する場合と、(2)ある定常状態から異なる定常状態へ遷移する場合などが想定されるが、本研究では、遷移現象を解析するための再現性の高い実験系が確立したことに意義があると考える。さらにこの系を用いて、新規の多能性幹細胞やグローバルな遺伝子発現低下を起こす細胞集団の発見、そしてＸ染色体不活性化に代表されるエピゲノム変動との関連を追及するための材料を提案したことについても、今後の広範な展開に繋がる学術的な意義があると考える。