Linking the Cell Cycle to Cell Fate Decisions.
Linking the Cell Cycle to Cell Fate Decisions.
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DOI：
10.1016/j.tcb.2015.07.007
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发表时间：
2015-10
影响因子：
19
通讯作者：
Dalton S
中科院分区：
文献类型：
--
作者：
Dalton S
多能干细胞在进行自我更新的同时，保留了向多种细胞类型分化的能力。它们还表现出一种不寻常的细胞周期调节模式，反映在细胞周期结构中G1期和g2期被截断。当个体多能干细胞暴露于特定线索时，它们会激活发育程序并重塑细胞周期，从而使G1的长度和整体细胞分裂时间增加。单个干细胞对促分化信号的反应具有显著的异质性，导致非同步分化。最近的证据表明，这种现象是由于细胞周期依赖机制限制了发育基因的初始激活到g1期。这表明了一个广泛的生物学机制，即多能细胞在G1过渡期间启动细胞命运决定。对分化状态的承诺机制及其与细胞周期的关系进行了讨论。
Pluripotent stem cells 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 pluripotent stem cells 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. Mechanisms underpinning commitment towards the differentiated state and its relationship to the cell cycle are discussed.