Noise is prevalent in biology and has been widely quantified using snapshot measurements. This static view obscures our understanding of dynamic noise properties and how these affect gene expression and cell state transitions. Using a CRISPR /Cas9 Zebrafish her6::Venus reporter combined with mathematical and in vivo experimentation, we explore how noise affects the protein dynamics of Her6, a basic helix‐loop‐helix transcriptional repressor. During neurogenesis, Her6 expression transitions from fluctuating to oscillatory at single‐cell level. We identify that absence of miR‐9 input generates high‐frequency noise in Her6 traces, inhibits the transition to oscillatory protein expression and prevents the downregulation of Her6. Together, these impair the upregulation of downstream targets and cells accumulate in a normally transitory state where progenitor and early differentiation markers are co‐expressed. Computational modelling and double smFISH of her6 and the early neurogenesis marker, elavl3 , suggest that the change in Her6 dynamics precedes the downregulation in Her6 levels. This sheds light onto the order of events at the moment of cell state transition and how this is influenced by the dynamic properties of noise. Our results suggest that Her/Hes oscillations, facilitated by dynamic noise optimization by miR‐9, endow progenitor cells with the ability to make a cell state transition.

中文翻译：

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miR-9 优化了噪声和 Her6 水平的动态特性，从而可以解码 Her6 振荡器。


噪声在生物学中普遍存在，并且已通过快照测量被广泛量化。这种静态视图模糊了我们对动态噪声特性以及它们如何影响基因表达和细胞状态转换的理解。使用 CRISPR /Cas9 斑马鱼her6::Venus报告基因，结合数学和体内实验，我们探索了噪声如何影响 Her6（一种基本的螺旋-环-螺旋转录抑制因子）的蛋白质动力学。在神经发生过程中，Her6 表达在单细胞水平上从波动转变为振荡。我们发现，缺乏 miR-9 输入会在 Her6 痕迹中产生高频噪声，抑制向振荡蛋白表达的转变并防止 Her6 的下调。总之，这些损害了下游靶标的上调，并且细胞在祖细胞和早期分化标记物共表达的正常短暂状态下积累。 Her6和早期神经发生标记物elavl3的计算模型和双 smFISH 表明 Her6 动力学的变化先于 Her6 水平的下调。这揭示了细胞状态转换时事件的顺序以及噪声的动态特性如何影响它。我们的结果表明，miR-9 的动态噪声优化促进了 Her/Hes 振荡，赋予祖细胞进行细胞状态转换的能力。