Abstract—One of the key regulators of hematopoietic stem cell (HSC) maintenance is cellular metabolism. Resting HSCs use anaerobic glycolysis as the main source of energy. During expansion and differentiation under conditions of steady state hematopoiesis, the energy needs of activated HSCs increase by many fold. To meet the increased demands, cells switch to mitochondrial oxidative phosphorylation, which is accompanied by an increase in reactive oxygen species (ROS) production. Here, the molecular mechanisms maintaining glycolysis in HSCs, as well as the factors determining the increase in metabolic activity and the transition to mitochondrial biogenesis during HSC activation are discussed. We focus on the role of HIF (hypoxia-inducible factor) proteins as key mediators of the cellular response to hypoxia, and also consider the phenomenon of extraphysiological oxygen shock (EPHOSS), leading to the forced differentiation of HSCs as well as methods of overcoming it. Finally, the role of fatty acid oxidation (FAO) in hematopoiesis is discussed. Understanding the metabolic needs of normal HSCs and precursors is crucial for the development of new treatments for diseases related to the hematopoietic and immune systems.

摘要：细胞代谢是造血干细胞（HSC）维持的关键调节因子之一。静息状态的 HSC 使用无氧糖酵解作为主要能量来源。在稳态造血条件下的扩增和分化过程中，活化的HSC的能量需求增加许多倍。为了满足增加的需求，细胞转向线粒体氧化磷酸化，这伴随着活性氧（ROS）产生的增加。在此，讨论了 HSC 中维持糖酵解的分子机制，以及决定 HSC 激活过程中代谢活性增加和向线粒体生物发生转变的因素。我们重点关注HIF（缺氧诱导因子）蛋白作为细胞对缺氧反应的关键介质的作用，并考虑导致HSC强制分化的生理外氧休克（EPHOSS）现象以及克服方法它。最后，讨论了脂肪酸氧化（FAO）在造血中的作用。了解正常造血干细胞和前体细胞的代谢需求对于开发造血和免疫系统相关疾病的新疗法至关重要。