Ito Keisuke
Ruth L and David S Gottesman Institute for Stem Cell and Regenerative Medicine Research and Departments of Cell Biology and Medicine, Albert Einstein College of Medicine.
Rinsho Ketsueki. 2018;59(7):909-914. doi: 10.11406/rinketsu.59.909.
Stem cells are self-renewing, either multipotent or unipotent, and they offer opportunities for stem cell-based therapies in the clinical setting. The mechanism underlying the division patterns of hematopoietic stem cells (HSCs) is one of the most fundamental biological questions. However, to date, analyses of individual HSC cell fate decisions have been restricted by the heterogeneity of available HSC-enriched fractions and the technical challenges of imaging HSC fate. Comprehensive research accompanied with genetic models, metabolomics analyses, and single-cell approaches have highlighted the critical contributions of metabolic control to HSC homeostasis. Consequently, the roles of mitochondrial metabolism in the HSC division symmetry have become a central focus of the current research. Nevertheless, we are only beginning to comprehend the metabolic requirements of stemness. This review summarizes the recent advances in our understanding of the intriguing relationship between mitochondrial metabolism and HSC fate decisions. In addition, this study highlights our recent findings regarding the contributions of the mitochondrial quality control by autophagy to HSC division balance. Elucidation of the metabolic cues governing HSC fate decisions should lead to new techniques of metabolic manipulation, which can shift the division balance of HSCs and offer effective targets in strategies against leukemia and will, thus, be of high clinical importance.
干细胞能够自我更新，具有多能性或单能性，为临床环境中基于干细胞的治疗提供了机会。造血干细胞（HSCs）分裂模式的潜在机制是最基本的生物学问题之一。然而，迄今为止，对单个造血干细胞命运决定的分析受到可用的富含造血干细胞组分的异质性以及对造血干细胞命运进行成像的技术挑战的限制。伴随遗传模型、代谢组学分析和单细胞方法的综合研究突出了代谢控制对造血干细胞稳态的关键作用。因此，线粒体代谢在造血干细胞分裂对称性中的作用已成为当前研究的核心焦点。尽管如此，我们才刚刚开始理解干性的代谢需求。这篇综述总结了我们在理解线粒体代谢与造血干细胞命运决定之间有趣关系方面的最新进展。此外，本研究突出了我们最近关于自噬对线粒体质量控制在造血干细胞分裂平衡中的贡献的发现。阐明控制造血干细胞命运决定的代谢线索应能带来新的代谢操纵技术，这些技术可以改变造血干细胞的分裂平衡，并为对抗白血病的策略提供有效的靶点，因此具有很高的临床重要性。
