Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Adv Exp Med Biol. 2019;1143:59-74. doi: 10.1007/978-981-13-7342-8_3.
One of the bottlenecks of the treatments for malignant hematopoietic disorders is the unavailability of sufficient amount of hematopoietic stem cells (HSCs). HSCs are considered to be originated from the aorta-gonad-mesonephros and gradually migrates into fetal liver and resides in a unique microenvironment/niche of bone marrow. Although many intrinsic and extrinsic factors (niche components) are reported to be involved in the origination, maturation, migration, and localization of HSCs at different developmental stages, the detailed molecular mechanisms still remain largely unknown. Previous studies have shown that intrinsic metabolic networks may be critical for the cell fate determinations of HSCs. For example, HSCs mainly utilize glycolysis as the main energy sources; oxidative phosphorylation is required for the homeostasis of HSCs; lipid or amino acid metabolisms may also sustain HSC stemness. Mechanistically, lots of regulatory pathways, such as MEIS1/HIF1A and PI3K/AKT/mTOR signaling, are found to fine-tune the different nutrient metabolisms and cell fate commitments of HSCs. However, more efforts are required for the optimization and establishment of precise metabolic techniques specific for the HSCs with relatively rare cell frequency and understanding of the basic metabolic properties and their underlying regulatory mechanisms of different nutrients (such as glucose) during the different developmental stages of HSCs.
恶性血液疾病治疗的一个瓶颈是缺乏足够数量的造血干细胞（HSCs）。HSCs 被认为起源于主动脉-性腺-中肾，并逐渐迁移到胎儿肝脏，并存在于骨髓的独特微环境/龛位中。尽管许多内在和外在因素（龛位成分）被报道参与了 HSCs 在不同发育阶段的起源、成熟、迁移和定位，但详细的分子机制仍在很大程度上未知。先前的研究表明，内在代谢网络可能对 HSCs 的细胞命运决定至关重要。例如，HSCs 主要利用糖酵解作为主要能量来源；氧化磷酸化是 HSCs 稳态所必需的；脂质或氨基酸代谢也可能维持 HSC 的干性。从机制上讲，许多调节途径，如 MEIS1/HIF1A 和 PI3K/AKT/mTOR 信号通路，被发现可以微调 HSCs 的不同营养代谢和细胞命运决定。然而，需要更多的努力来优化和建立针对 HSCs 的精确代谢技术，这些技术针对的是细胞频率相对较低的 HSCs，并了解不同营养物质（如葡萄糖）在 HSCs 的不同发育阶段的基本代谢特性及其潜在的调节机制。
