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Updated: Feb 22, 2026

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单细胞参数推理揭示了合成哺乳动物基因表达中的动态异质性

Joshua Azukas¹, Rafał Krzysztoń¹, Christopher Helenek¹

¹Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA; The Louis and Beatrice Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York 11794, United States.

Biophysical journal

|February 21, 2026

概括

负反基因电路可以减少基因表达噪声. 这项研究量化了反强度如何影响蛋白质水平随时间变化和跨细胞群体的变化,使用先进的成像和推断方法.

科学领域:

分子生物学分子生物学
系统生物学系统生物学
生物物理学的生物物理.

背景情况:

基因表达表现出自然波动 ("噪声"),影响关键的细胞过程,如分化和亡.
负反基因电路用于减轻单基因表达噪声,但它们对哺乳动物时间和人口水平噪声的定量影响尚不清楚.

研究的目的:

在哺乳动物细胞中定量表征时间和种群层次的基因表达噪声.
为了研究转录负反如何修改这种噪音.
为了比较反和构成性基因表达系统之间的噪声概况.

主要方法:

开发一个综合框架,将单细胞阵列的活细胞成像 (LISCA) 与无概率推断相结合.
在单细胞分辨率和时间域中对随机基因表达的表征.
推断动力速率参数以验证混合随机/决定模型.

主要成果:

在时间噪声 (CVt) 和人口级噪声 (CVp) 之间观察到显著的差异.
负反强度和合作性被证明可以定量控制平均蛋白质水平及其变化.
该研究验证了变化系数 (CV) 与平均蛋白质水平关系的预测模型.

结论:

转录性负反在调节时间和人口层面的基因表达噪声方面发挥着至关重要的作用.
反强度和合作性是决定蛋白质变异范围的关键参数,这些参数在一个人群内和随着时间的推移而变化.
开发的框架为剖析复杂生物系统中随机基因表达动态提供了强大的工具.

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