Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies

Nico Battich, Joep Beumer, Buys de Barbanson, Lenno Krenning, Chloé S Baron, Marvin E Tanenbaum, Hans Clevers, Alexander van Oudenaarden

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1151-1156
Number of pages6
JournalScience
Volume367
Issue number6482
DOIs
Publication statusPublished - 06 Mar 2020

Keywords

  • Animals
  • Humans
  • Indicators and Reagents/chemistry
  • K562 Cells
  • Mice
  • RNA Stability
  • RNA, Messenger/metabolism
  • Sequence Analysis, RNA/methods
  • Single-Cell Analysis/methods
  • Transcription, Genetic
  • Uridine/analogs & derivatives

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