Single-cell Timelapse measurement of metabolic change during stem cell differentiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14721
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: The University of Tokyo (2019-2020); Institute of Physical and Chemical Research (2018)
• Principal Investigator: Yaginuma Hideyuki 東京大学, 大学院工学系研究科(工学部), 特任研究員 (10733222)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ATP / 細胞イメージング / 代謝計測 / 蛍光プローブ

Outline of Final Research Achievements

Intracellular energy production pathways, such as oxidative phosphorylation and glycolysis, are closely related to intracellular metabolic conditions. With conventional ATP measurement methods, it has been difficult to accurately quantify intracellular ATP concentration at the single cell level. In this study, we examined how the metabolic state changes depending on the culture and differentiation status of cells using a ratiometric fluorescent ATP indicator protein "QUEEN" that quantitatively measures the intracellular ATP concentration. In this study, we examined how the metabolic state of undifferentiated cells changes depending on their culture and differentiation status. We succeeded in finding that the metabolic state changes significantly depending on the culture state of the cells, and also elucidated the possibility of interaction of the metabolic state between embryonic stem cells.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

ATPは、さまざまな細胞内の反応の進行に必要であり、細胞の代謝状態のパラメーターとして重要である。ATPのような代謝物質の濃度は細胞の運命決定に大きく関わっていると考えられる。本研究により、細胞が性質をかえていくに従って細胞内の代謝状態に多様な状態が現れることを単一細胞計測により明らかにした。また、細胞同士が作用しあうことによって代謝状態が変化する可能性も示された。これらの結果から、生物の細胞集団がどのように多様な細胞種が生み出されるか、またそれらが協調して個体を作り上げていくか、というメカニズムの解明に寄与したと考えられる。