Siu Ka Tat, Minella Alex C
Northwestern University Feinberg School of Medicine, 303 East Superior Street, Lurie 5-115, 60611, Chicago, IL, USA.
Adv Exp Med Biol. 2014;844:189-200. doi: 10.1007/978-1-4939-2095-2_9.
To maintain hematologic homeostasis, hematopoietic stem cells (HSCs) undergo multiple rounds of cell division throughout their lives. Under steady-state conditions, adult HSCs are relatively quiescent and reside primarily in hypoxic bone marrow niches. In response to physiologic stimuli, normal HSCs either reenter the cell division cycle or remain in quiescence. A large body of work has focused on understanding the mechanistic underpinnings balancing differentiation against self-renewal programs in cycling HSCs. Numerous reports from genetically engineered mouse models harboring mutations in key pathways governing proliferation control, DNA damage responses, and metabolic regulation indicate the critical roles these processes play in determining HSC self-renewing versus blood-lineage-reconstituting divisions. In this chapter, we integrate these findings and highlight the cellular networks that control HSC function and fitness by regulating HSC cycling.
为维持血液学稳态，造血干细胞（HSCs）在其一生中会经历多轮细胞分裂。在稳态条件下，成年造血干细胞相对静止，主要存在于低氧的骨髓龛中。响应生理刺激时，正常造血干细胞要么重新进入细胞分裂周期，要么保持静止状态。大量研究致力于理解调控循环造血干细胞中分化与自我更新程序平衡的机制基础。来自基因工程小鼠模型的众多报告显示，在控制增殖、DNA损伤反应和代谢调节的关键途径中存在突变，这表明这些过程在决定造血干细胞自我更新与血液谱系重建分裂中发挥着关键作用。在本章中，我们整合了这些发现，并强调了通过调节造血干细胞循环来控制其功能和健康状态的细胞网络。
