Cellular asymmetry and individuality in directional sensing
Cellular asymmetry and individuality in directional sensing
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DOI：
10.1073/pnas.0601909103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
van Oudenaarden, Alexander
中科院分区：
文献类型：
--
作者：
Samadani, Azadeh;Mettetal, Jerome;van Oudenaarden, Alexander
一般认为，当暴露于相同的环境时，同基因群体中的单个细胞表现出相同的行为。然而，越来越清楚的是，即使在遗传上相同的群体中，细胞行为也会在细胞之间显着变化。在这里，我们探讨这种变化的梯度感应反应的网骨藻细胞暴露于重复的时空脉冲的化学引诱物。我们的实验表明，单细胞的反应是高度可重复的脉冲。相比之下，从细胞到细胞观察到响应方向和幅度的大的可变性，即使当不同的细胞暴露于相同的脉冲时。首先，这些结果表明，梯度传感网络具有固有的不对称性，可以显着影响细胞忠实地感知细胞外信号方向的能力（细胞不对称性）。其次，我们发现这种不对称性的大小在细胞之间变化很大。一些细胞能够准确地遵循细胞外刺激的方向，而在其他细胞中，细胞内不对称占主导地位，导致极化轴独立于细胞外信号的方向（细胞个体性）。我们将这些实验结果整合到一个模型中，该模型将细胞检测到的有效信号视为细胞外信号和不对称细胞内信号的产物。通过这个模型，我们成功地预测了人口反应。这种细胞的个体性和不对称性可能从根本上限制了信号检测的保真度;然而，相反，它可能是有益的，因为它使同基因群体的表型多样化。
It is generally assumed that single cells in an isogenic population, when exposed to identical environments, exhibit the same behavior. However, it is becoming increasingly clear that, even in a genetically identical population, cellular behavior can vary significantly among cells. Here we explore this variability in the gradient-sensing response of Dictyostelium cells when exposed to repeated spatio-temporal pulses of chemoattractant. Our experiments show the response of a single cell to be highly reproducible from pulse to pulse. In contrast, a large variability in the response direction and magnitude is observed from cell to cell, even when different cells are exposed to the same pulse. First, these results indicate that the gradient-sensing network has inherent asymmetries that can significantly impact the ability of cells to faithfully sense the direction of extracellular signals (cellular asymmetry). Second, we find that the magnitude of this asymmetry varies greatly among cells. Some cells are able to accurately follow the direction of an extracellular stimulus, whereas, in other cells, the intracellular asymmetry dominates, resulting in a polarization axis that is independent of the direction of the extracellular cue (cellular individuality). We integrate these experimental findings into a model that treats the effective signal a cell detects as the product of the extracellular signal and the asymmetric intracellular signal. With this model we successfully predict the population response. This cellular individuality and asymmetry might fundamentally limit the fidelity of signal detection; in contrast, however, it might be beneficial by diversifying phenotypes in isogenic populations.