Temporal competition between differentiation programs determines cell fate choice.

Temporal competition between differentiation programs determines cell fate choice.
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DOI:
10.1038/msb.2011.88
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发表时间:
2011-12-06
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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--
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多能分化,即细胞采取几种可能的命运之一,发生在从细菌到哺乳动物的各种系统中。这个决策过程是由细胞中同时运行的多个分化程序驱动的。这些程序如何相互作用来管理细胞命运的选择是知之甚少。为了研究这个问题,我们同时测量了单个枯草芽孢杆菌细胞中竞争性孢子形成和感受态程序的活性。这种方法表明,这些竞争性分化程序独立进行,在决策点之前没有交叉调节。细胞似乎通过两个程序之间相对时间的差异来达成命运选择。为了测试这个提出的动态机制,我们改变了相对的时间工程人工交叉调节之间的孢子形成和能力电路。结果表明,一个简单的模型,不需要检查点或复杂的交叉调节细胞决策之前。相反,细胞命运的选择似乎是分化程序之间的“分子竞赛”的结果,这些程序在时间上竞争,为决策提供了一个简单的动态机制。
Multipotent differentiation, where cells adopt one of several possible fates, occurs in diverse systems ranging from bacteria to mammals. This decision-making process is driven by multiple differentiation programs that operate simultaneously in the cell. How these programs interact to govern cell fate choice is poorly understood. To investigate this issue, we simultaneously measured activities of the competing sporulation and competence programs in single Bacillus subtilis cells. This approach revealed that these competing differentiation programs progress independently without cross-regulation before the decision point. Cells seem to arrive at a fate choice through differences in the relative timing between the two programs. To test this proposed dynamic mechanism, we altered the relative timing by engineering artificial cross-regulation between the sporulation and competence circuits. Results suggest a simple model that does not require a checkpoint or intricate cross-regulation before cellular decision-making. Rather, cell fate choice appears to be the outcome of a ‘molecular race’ between differentiation programs that compete in time, providing a simple dynamic mechanism for decision-making.
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