Meacham Corbin E, DeVilbiss Andrew W, Morrison Sean J
Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Paediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Rev Mol Cell Biol. 2022 Jun;23(6):428-443. doi: 10.1038/s41580-022-00462-1. Epub 2022 Feb 28.
Metabolism has been studied mainly in cultured cells or at the level of whole tissues or whole organisms in vivo. Consequently, our understanding of metabolic heterogeneity among cells within tissues is limited, particularly when it comes to rare cells with biologically distinct properties, such as stem cells. Stem cell function, tissue regeneration and cancer suppression are all metabolically regulated, although it is not yet clear whether there are metabolic mechanisms unique to stem cells that regulate their activity and function. Recent work has, however, provided evidence that stem cells do have a metabolic signature that is distinct from that of restricted progenitors and that metabolic changes influence tissue homeostasis and regeneration. Stem cell maintenance throughout life in many tissues depends upon minimizing anabolic pathway activation and cell division. Consequently, stem cell activation by tissue injury is associated with changes in mitochondrial function, lysosome activity and lipid metabolism, potentially at the cost of eroding self-renewal potential. Stem cell metabolism is also regulated by the environment: stem cells metabolically interact with other cells in their niches and are able to sense and adapt to dietary changes. The accelerating understanding of stem cell metabolism is revealing new aspects of tissue homeostasis with the potential to promote tissue regeneration and cancer suppression.
新陈代谢主要是在培养细胞中或在体内全组织或整个生物体水平上进行研究的。因此,我们对组织内细胞间代谢异质性的理解有限,尤其是对于具有生物学独特特性的稀有细胞,如干细胞。干细胞功能、组织再生和癌症抑制均受代谢调节,尽管目前尚不清楚是否存在调节干细胞活性和功能的独特代谢机制。然而,最近的研究提供了证据,表明干细胞确实具有与受限祖细胞不同的代谢特征,并且代谢变化会影响组织稳态和再生。许多组织中干细胞的终生维持依赖于尽量减少合成代谢途径的激活和细胞分裂。因此,组织损伤引起的干细胞激活与线粒体功能、溶酶体活性和脂质代谢的变化有关,这可能是以消耗自我更新潜能为代价的。干细胞代谢也受环境调节:干细胞在其微环境中与其他细胞发生代谢相互作用,并能够感知和适应饮食变化。对干细胞代谢的深入理解正在揭示组织稳态的新方面,具有促进组织再生和癌症抑制的潜力。