Immunology Discovery, Genentech, Inc. 1 DNA Way, South San Francisco, CA, 94080, USA.
Free Radic Biol Med. 2021 Mar;165:38-53. doi: 10.1016/j.freeradbiomed.2021.01.034. Epub 2021 Jan 21.
Hematopoietic stem cells (HSCs) are responsible for life-long production of blood and immune cells. HSC transplantation (HSCT) is the original cell therapy which can cure hematological disorders but also has the potential to treat other diseases if technical and safety barriers are overcome. To maintain homeostatic hematopoiesis or to restore hematopoiesis during transplantation HSCs must perform both self-renewal, replication of themselves, and differentiation, generation of mature blood and immune cells. These are just two of the cell fate choices HSCs have; the transitional phases where HSCs undergo these cell fate decisions are regulated by reduction-oxidation (redox) signaling, mitochondrial activity, and cellular metabolism. Recent studies revealed that mitochondria, a key source of redox signaling components, are central to HSC cell fate decisions. Here we highlight how mitochondria serve as hubs in HSCs to manage redox signaling and metabolism and thus guide HSC fate choices. We focus on how mitochondrial activity is modulated by their clearance, biogenesis, dynamics, distribution, and quality control in HSCs. We also note how modulating mitochondria in HSCs can help overcome technical barriers limiting further use of HSCT.
造血干细胞（HSCs）负责终生产生血液和免疫细胞。HSC 移植（HSCT）是最初的细胞疗法，不仅可以治愈血液系统疾病，而且如果克服了技术和安全障碍，还有可能治疗其他疾病。为了维持稳态造血或在移植期间恢复造血，HSCs 必须执行自我更新、自身复制和分化、生成成熟的血液和免疫细胞这两个细胞命运选择。这只是 HSCs 所具有的两个细胞命运选择；HSCs 进行这些细胞命运决策的过渡阶段受氧化还原（redox）信号、线粒体活性和细胞代谢的调节。最近的研究表明，线粒体是 redox 信号成分的主要来源，是 HSC 细胞命运决策的核心。在这里，我们强调了线粒体如何作为 HSCs 中的枢纽来管理 redox 信号和代谢，从而指导 HSC 命运选择。我们专注于 HSCs 中线粒体活性如何通过其清除、生物发生、动力学、分布和质量控制来调节。我们还注意到如何调节 HSCs 中的线粒体可以帮助克服限制 HSCT 进一步应用的技术障碍。
