Metabolic system of hematopoietic stem cells and its age-related changes revealed by real-time ATP quantification in living cells

Abstract

Hematopoietic stem cells' (HSCs) metabolic dynamics regulate cell fate and differentiation. To maintain the stemness of HSCs, it is necessary to maintain an appropriate balance of adenosine triphosphate (ATP) production by the glycolytic system and mitochondria. In conventional intracellular ATP measurement, snapshot analysis is performed after the lysis of a large number of cells, resulting in the loss of single-cell level and spatiotemporal information. To overcome this technical limitation, we recently developed a methodology for measuring ATP concentration in living HSCs using knock-in mice of an intracellular ATP concentration biosensor called GO-ATeam2, which employs the principle of Förster resonance energy transfer. The current understanding of metabolism in HSCs, the metabolic dependence of HSCs revealed by the GO-ATeam2 system, and the prospects for novel metabolic measurement techniques in the future are reviewed in this paper.