Center for Quantitative Biology and Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.
Mol Syst Biol. 2020 May;16(5):e9335. doi: 10.15252/msb.20199335.
Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions and whether it could be neutralized by cellular reactions. Here, using fluorescent protein (FP) maturation as a model biochemical reaction, we explored how cellular reactions might combat global extrinsic noise in mammalian cells. We developed a novel single-cell assay to systematically quantify the maturation rate and the associated noise for over a dozen FPs. By exploiting the variation in the maturation rate for different FPs, we inferred that global extrinsic noise could be temporally filtered by maturation reactions, and as a result, the noise levels for slow-maturing FPs are lower compared to fast-maturing FPs. This mechanism is validated by directly perturbing the maturation rates of specific FPs and measuring the resulting noise levels. Together, our results revealed a potentially general principle governing extrinsic noise propagation, where timescale separation allows cellular reactions to cope with dynamic global extrinsic noise.
最近的研究表明，源于细胞内生化环境随机性的全球外在噪声在异质细胞生理学中起着关键作用。然而，外在噪声如何动态地影响下游反应，以及细胞反应是否可以中和这种噪声，在很大程度上仍然不清楚。在这里，我们使用荧光蛋白 (FP) 成熟作为模型生化反应，探索了细胞反应如何在哺乳动物细胞中对抗全球外在噪声。我们开发了一种新的单细胞测定法，系统地量化了十几个 FP 的成熟率及其相关噪声。通过利用不同 FP 的成熟率的变化，我们推断出成熟反应可以对全球外在噪声进行时间滤波，因此，与快速成熟的 FP 相比，成熟速度较慢的 FP 的噪声水平较低。通过直接扰动特定 FP 的成熟率并测量产生的噪声水平，验证了这一机制。总的来说，我们的研究结果揭示了一个潜在的普遍原则，即外在噪声的传播，其中时间尺度的分离使细胞反应能够应对动态的全球外在噪声。
