Institute of Biology (IBL), Leiden University, Sylvius Laboratory, ylviusweg 72, 2333 BE Leiden, The Netherlands.
Front Biosci (Landmark Ed). 2014 Jun 1;19(6):1003-14. doi: 10.2741/4263.
Stem cells have the unique ability to both maintain the stem cell population via self-renewal and give rise to differentiated cells. The balance between these options is very delicate and important for the short- and long-term maintenance of tissue homeostasis in an organism. Pathways involved in integrating environmental cues and in directing energy metabolism play an important role in the fate decisions of stem cells. In this review, we give an overview of the effects of cellular and systemic metabolic states on stem-cell fate in both embryonic and in adult stem cell populations, with a particular emphasis on cell-cycle regulation. We discuss the major pathways implicated in sensing energetic status and regulating metabolism, including: the mTOR pathway, Forkhead-box-O transcription factors (FoxOs), Sirtuins, reactive oxygen species (ROS), AMP-activated kinase (AMPK) and LKB1, the mTOR pathway and hypoxia inducible factors (HIFs). Given the importance of a correct balance between self-renewal and differentiation, understanding the mechanisms that drive stem-cell fate in different metabolic conditions will provide more insight in stem cell biology in both health and disease.
干细胞具有独特的自我更新能力，可产生分化细胞。这两种选择之间的平衡对于生物体组织内稳态的短期和长期维持非常重要。整合环境线索和指导能量代谢的途径在干细胞的命运决定中起着重要作用。在这篇综述中，我们概述了细胞和全身代谢状态对胚胎和成年干细胞群体中干细胞命运的影响，特别强调了细胞周期调控。我们讨论了参与感知能量状态和调节代谢的主要途径，包括：mTOR 途径、叉头框 O 转录因子（FoxOs）、沉默调节蛋白、活性氧（ROS）、AMP 激活的蛋白激酶（AMPK）和 LKB1、mTOR 途径和缺氧诱导因子（HIFs）。鉴于自我更新和分化之间平衡的重要性，了解不同代谢条件下驱动干细胞命运的机制将为健康和疾病中的干细胞生物学提供更多的见解。
