13C-metabolic flux analysis and fate control for differentiatable cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15100
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Osaka University
• Principal Investigator: Okahashi Nobuyuki 大阪大学, 大学院情報科学研究科, 准教授 (30802748)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 13C代謝フラックス解析 / 細胞分化 / 分化制御 / 中心炭素代謝 / 補酵素バランス

Outline of Final Research Achievements

The development of technology to induce differentiation into cells with specific functions is an important issue in regenerative medicine. In this study, we developed 13C metabolic flux analysis, which can measure metabolic reaction rate, to quantitatively compare the metabolic state of cells before and after differentiation. The metabolic models of HL-60, a neutrophil-like cell line, and THP-1, a macrophage-like cell lines were examined. Then flux distribution before and after differentiation was successfully calculated using the developed model. Furthermore, we showed that cell differentiation can be externally controlled by inhibiting reactions activated during differentiation.

Free Research Field

代謝工学

Academic Significance and Societal Importance of the Research Achievements

本研究で最適化した13C代謝フラックス解析法は、これまで不明であった終末分化した細胞の代謝状態を定量的に明らかできる点で新規性があり、分化前後での細胞の代謝の変化をフラックスレベルで明らかにした先駆的な事例である。今後、分化する他の種類の細胞の代謝の変化を計測するための基盤技術としての活用が見込まれ、細胞分化のメカニズム解明や、再生医療などにおける細胞の分化制御に貢献できる可能性がある。