Dalton Stephen
Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, Paul D. Coverdell Center for Biomedical and Health Sciences, University of Georgia, 500 DW Brooks Drive, Athens, GA 30602, USA.
Trends Cell Biol. 2015 Oct;25(10):592-600. doi: 10.1016/j.tcb.2015.07.007.
Pluripotent stem cells (PSCs) retain the ability to differentiate into a wide range of cell types while undergoing self-renewal. They also exhibit an unusual mode of cell cycle regulation, reflected by a cell cycle structure where G1 and G2 phases are truncated. When individual PSCs are exposed to specification cues, they activate developmental programs and remodel the cell cycle so that the length of G1 and overall cell division times increase. The response of individual stem cells to pro-differentiation signals is strikingly heterogeneous, resulting in asynchronous differentiation. Recent evidence indicates that this phenomenon is due to cell cycle-dependent mechanisms that restrict the initial activation of developmental genes to the G1 phase. This suggests a broad biological mechanism where multipotent cells are 'primed' to initiate cell fate decisions during their transition through G1. Here, I discuss mechanisms underpinning the commitment towards the differentiated state and its relation to the cell cycle.
多能干细胞（PSCs）在自我更新的同时，保留了分化为多种细胞类型的能力。它们还表现出一种不寻常的细胞周期调控模式，其细胞周期结构的特点是G1期和G2期被缩短。当单个PSCs暴露于分化诱导信号时，它们会激活发育程序并重塑细胞周期，从而使G1期的长度和整个细胞分裂时间增加。单个干细胞对促分化信号的反应具有显著的异质性，导致分化不同步。最近的证据表明，这种现象是由于细胞周期依赖性机制，该机制将发育基因的初始激活限制在G1期。这提示了一种广泛的生物学机制，即多能细胞在通过G1期的转变过程中被“启动”以启动细胞命运决定。在此，我将讨论支持细胞向分化状态转变的机制及其与细胞周期的关系。
