Inferring cell differentiation process based on phylogenetic analysis of histone modifications of human cells

• Project/Area Number: 16K07458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Evolutionary biology
• Research Institution: Hokkaido University
• Principal Investigator: Koyanagi Kanako 北海道大学, 情報科学研究院, 准教授 (20362840)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 系統解析 / 細胞分化 / エピジェネティクス / ヒストン修飾 / 細胞系譜 / 祖先推定 / 祖先復元 / 発生・分化 / 系統進化

Outline of Final Research Achievements

For understanding the development of animals, it is important to reveal the landscape of epigenetic changes in cells during differentiation process. However, analyzing whole differentiation processes in various cell types is laborious and impossible for some organisms. In this study, phylogenetic analysis is applied to reconstruct developmental processes based on the developmental changes of epigenomes of differentiated cells. Using epigenomes of eight types of differentiated human hematopoietic cells, ancestral state estimation based on a phylogenetic tree was applied to map the epigenomic changes of six kinds of histone modifications onto the hierarchical cell differentiation process of hematopoiesis. As a result, it was shown that this approach could infer an appropriate landscape of histone modification changes during hematopoiesis.

Academic Significance and Societal Importance of the Research Achievements

エピジェネティック修飾の状態は、細胞内の各遺伝子の発現状態を反映していると考えられることから、特に発生過程の実験データ取得が困難な生物の個体発生過程の理解に役立てられることが期待される。また、細胞分化の各過程でエピジェネティック修飾に変化がみられた遺伝子群は、特定の系列の細胞を分化させるために必要な遺伝子候補であるので、分化誘導の応用に貢献することも期待される。

Research Products

• [Journal Article] Inferring changes in histone modification during cell differentiation by ancestral state estimation based on phylogenetic trees of cell types: Human hematopoiesis as a model case (2019)
  • Author(s): Koyanagi KO
  • Journal Title: Gene: X Volume: 3 Pages: 100021-100021
  • DOI: 10.1016/j.gene.2019.100021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Inferring cell differentiation processes based on phylogenetic analysis of genome-wide epigenetic information (2018)
  • Author(s): Kanako O. Koyanagi
  • Organizer: Society for Molecular Biology and Evolution
  • Int'l Joint Research
• [Presentation] Inferring cell differentiation processes based on phylogenetic analysis of genome-wide epigenetic information (2017)
  • Author(s): Kanako O. Koyanagi
  • Organizer: CDB Symposium 2017
  • Place of Presentation: 理化学研究所 多細胞システム形成研究センター（神戸市）
  • Year and Date: 2017-03-27
  • Int'l Joint Research
• [Presentation] エピゲノム情報の系統解析による細胞分化過程の推定 -哺乳類の血球系細胞分化をモデルとして (2017)
  • Author(s): 小柳香奈子
  • Organizer: 分子生物学会
  • Invited