Treichel Sydney, Filippi Marie-Dominique
Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, United States.
University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Front Cell Dev Biol. 2023 Aug 14;11:1231735. doi: 10.3389/fcell.2023.1231735. eCollection 2023.
Hematopoietic stem cells (HSCs) have the properties to self-renew and/or differentiate into any blood cell lineages. In order to balance the maintenance of the stem cell pool with supporting mature blood cell production, the fate decisions to self-renew or to commit to differentiation must be tightly controlled, as dysregulation of this process can lead to bone marrow failure or leukemogenesis. The contribution of the cell cycle to cell fate decisions has been well established in numerous types of stem cells, including pluripotent stem cells. Cell cycle length is an integral component of hematopoietic stem cell fate. Hematopoietic stem cells must remain quiescent to prevent premature replicative exhaustion. Yet, hematopoietic stem cells must be activated into cycle in order to produce daughter cells that will either retain stem cell properties or commit to differentiation. How the cell cycle contributes to hematopoietic stem cell fate decisions is emerging from recent studies. Hematopoietic stem cell functions can be stratified based on cell cycle kinetics and divisional history, suggesting a link between Hematopoietic stem cells activity and cell cycle length. Hematopoietic stem cell fate decisions are also regulated by asymmetric cell divisions and recent studies have implicated metabolic and organelle activity in regulating hematopoietic stem cell fate. In this review, we discuss the current understanding of the mechanisms underlying hematopoietic stem cell fate decisions and how they are linked to the cell cycle.
造血干细胞（HSCs）具有自我更新和/或分化为任何血细胞谱系的特性。为了平衡干细胞池的维持与支持成熟血细胞的产生，自我更新或决定分化的命运抉择必须受到严格控制，因为这一过程的失调会导致骨髓衰竭或白血病发生。细胞周期对细胞命运抉择的作用在包括多能干细胞在内的多种干细胞类型中已得到充分证实。细胞周期长度是造血干细胞命运的一个重要组成部分。造血干细胞必须保持静止以防止过早的复制性耗竭。然而，造血干细胞必须被激活进入细胞周期，以便产生要么保留干细胞特性要么决定分化的子代细胞。细胞周期如何影响造血干细胞命运抉择正从最近的研究中逐渐显现。造血干细胞功能可根据细胞周期动力学和分裂历史进行分层，这表明造血干细胞活性与细胞周期长度之间存在联系。造血干细胞命运抉择也受到不对称细胞分裂的调控，并且最近的研究表明代谢和细胞器活性在调节造血干细胞命运中发挥作用。在这篇综述中，我们讨论了目前对造血干细胞命运抉择潜在机制的理解以及它们如何与细胞周期相联系。
