Memory and modularity in cell-fate decision making.

Memory and modularity in cell-fate decision making.
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细胞命运决策中的记忆和模块化。

DOI:
10.1038/nature12804
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发表时间:
2013-11-28
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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基因相同的细胞共享一个环境可以表现出明显不同的表型。人们通常不清楚这种变异在多大程度上源于偶然、外部信号或单个细胞试图实施自主的表型程序。通过对数千个细胞在恒定条件下连续数百代的观察,我们剖析了枯草芽孢杆菌在孤立、运动状态和链状、无柄状态之间的随机决策。运动状态是无记忆的,没有表现出对在状态中花费的时间的自主控制,而链接是严格计时的。定时加强了处于多细胞状态的相关细胞之间的协调。此外,我们还表明,控制决定的三种蛋白质调节电路是模块化的,因为链的启动和维持是基因上可分离的功能。由于同一启动途径的刺激触发了生物膜的形成,我们认为自主计时允许对外部信号可以延伸的多细胞的试验承诺。
Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. The motile state is memoryless, exhibiting no autonomous control over the time spent in the state, whereas chaining is tightly timed. Timing enforces coordination among related cells in the multicellular state. Further, we show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.
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