Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Curr Opin Hematol. 2021 Jul 1;28(4):262-268. doi: 10.1097/MOH.0000000000000644.
Hematopoietic stem cells (HSCs) are in an inactive quiescent state for most of their life. To replenish the blood system in homeostasis and after injury, they activate and divide. HSC daughter cells must then decide whether to return to quiescence and metabolic inactivity or to activate further to proliferate and differentiate and replenish lost blood cells. Although the regulation of HSC activation is not well understood, recent discoveries shed new light on involved mechanisms including asymmetric cell division (ACD).
HSC metabolism has emerged as a regulator of cell fates. Recent evidence suggests that cellular organelles mediating anabolic and catabolic processes can be asymmetrically inherited during HSC divisions. These include autophagosomes, mitophagosomes, and lysosomes, which regulate HSC quiescence. Their asymmetric inheritance has been linked to future metabolic and translational activity in HSC daughters, showing that ACD can regulate the balance between HSC (in)activity.
We discuss recent insights and remaining questions in how HSCs balance activation and quiescence, with a focus on ACD.
造血干细胞（HSCs）在其大部分生命周期中处于非活跃的静息状态。为了在体内平衡和损伤后补充血液系统，它们会激活和分裂。HSC 子细胞随后必须决定是返回静息和代谢不活跃状态，还是进一步激活以增殖和分化并补充丢失的血细胞。尽管 HSC 激活的调节机制尚不清楚，但最近的发现揭示了涉及的机制，包括不对称细胞分裂（ACD）。
HSC 代谢已成为细胞命运的调节者。最近的证据表明，在 HSC 分裂过程中，参与合成代谢和分解代谢过程的细胞细胞器可以不对称地遗传。这些细胞器包括自噬体、线粒体自噬体和溶酶体，它们调节 HSC 的静息状态。它们的不对称遗传与 HSC 子细胞未来的代谢和翻译活性有关，表明 ACD 可以调节 HSC（in）活性的平衡。
我们讨论了 HSCs 如何平衡激活和静息状态的最新见解和遗留问题，重点是 ACD。
