TY - JOUR
T1 - Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies
AU - Battich, Nico
AU - Beumer, Joep
AU - De Barbanson, Buys
AU - Krenning, Lenno
AU - Baron, Chloé S.
AU - Tanenbaum, Marvin E.
AU - Clevers, Hans
AU - Van Oudenaarden, Alexander
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/3/13
Y1 - 2020/3/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081530491&partnerID=8YFLogxK
M3 - Article
C2 - 32139547
AN - SCOPUS:85081530491
SN - 0036-8075
VL - 367
SP - 1151
EP - 1156
JO - Science
JF - Science
IS - 6483
ER -