Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies
Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies
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DOI：
10.1126/science.aax3072
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发表时间：
2020-03-06
期刊：
影响因子：
56.9
通讯作者：
van Oudenaarden, Alexander
中科院分区：
文献类型：
--
作者：
Battich, Nico;Beumer, Joep;van Oudenaarden, Alexander
哺乳动物细胞中信使RNA水平的调节可以通过调节合成和降解速率来实现。大量的代谢RNA标记实验已经使用相对同质的细胞群量化了这些速率。然而，为了在复杂的动力学过程中确定这些速率，例如在细胞分化期间，需要单细胞分辨率。因此，我们开发了一种方法，同时定量代谢标记和预先存在的未标记的转录在数千个单独的细胞。我们确定了在细胞周期和肠干细胞分化过程中的合成和降解速率，揭示了主要的调控策略。这些策略对于控制基因表达的动态范围和精确度具有不同的结果。这些发现推进了我们对异质群体中单个细胞如何塑造其基因表达动态的理解。
The regulation of messenger RNA levels in mammalian cells can be achieved by the modulation of synthesis and degradation rates. Metabolic RNA-labeling experiments in bulk have quantified these rates using relatively homogeneous cell populations. However, to determine these rates during complex dynamical processes, for instance during cellular differentiation, single-cell resolution is required. Therefore, we developed a method that simultaneously quantifies metabolically labeled and preexisting unlabeled transcripts in thousands of individual cells. We determined synthesis and degradation rates during the cell cycle and during differentiation of intestinal stem cells, revealing major regulatory strategies. These strategies have distinct consequences for controlling the dynamic range and precision of gene expression. These findings advance our understanding of how individual cells in heterogeneous populations shape their gene expression dynamics.