The new metabolic needs of hematopoietic stem cells.
The new metabolic needs of hematopoietic stem cells.
复制标题
造血干细胞的新陈代谢需求。
DOI：
10.1097/moh.0000000000000719
复制
发表时间：
2022-07-01
影响因子：
3.2
通讯作者：
Filippi, Marie-Dominique
中科院分区：
文献类型：
--
作者：
Bartram, James;Filippi, Marie-Dominique
造血干细胞 (HSC) 具有很高的再生潜力，可以在稳态或应激条件下在整个生命过程中提供成熟的血细胞。造血干细胞被认为在静止状态时依赖糖酵解，并在激活期间切换到氧化磷酸化以满足其代谢需求。最近，一系列重要的研究揭示了更高程度的复杂性，远远超出了糖酵解和氧化磷酸化之间的二分法。本综述的目的是总结最近的研究结果，强调 HSC 稳态的多方面代谢要求。新的证据表明溶酶体分解代谢活性和非经典视黄酸途径在维持 HSC 静止和干性方面的重要性。 HSC 激活进入循环似乎伴随着糖酵解-线粒体偶联和合成代谢途径的转变，包括 Myc、天冬氨酸介导的嘌呤合成。在过去的两年中，对 HSC 代谢的了解显着增加，并揭示了 HSC 在静止和激活状态下的意外需求。了解 HSC 如何利用新陈代谢来发挥其功能将为基于 HSC 的治疗提供新的机会。
Hematopoietic stem cells (HSCs) are endowed with high regenerative potential to supply mature blood cells throughout life, under steady state or stress conditions. HSCs are thought to rely on glycolysis when in a quiescent state and to switch to oxidative phosphorylation to meet their metabolic needs during activation. Recently, a series of important studies reveals a higher degree of complexity that goes well beyond the dichotomy between glycolysis and oxidative phosphorylation. The purpose of this review is to summarize the recent findings highlighting the multifaceted metabolic requirements of HSC homeostasis. Emerging evidence points to the importance of lysosomal catabolic activity and non-canonical retinoic acid pathway in maintaining HSC quiescence and stemness. HSC activation into cycle seems to be accompanied by a switch to glycolysis-mitochondrial coupling and to anabolic pathways, including Myc, aspartate-mediated purine synthesis. Knowledge of metabolism of HSCs has dramatically increased in the past 2 years and reveals unexpected needs of HSCs during both their quiescent and activated state. Understanding how HSCs use metabolism for their functions will offer new opportunity for HSC-based therapies.