Cellular noise

  • Article
    | Open Access

    The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

    • Katjana Tantale
    • , Encar Garcia-Oliver
    •  & Edouard Bertrand
  • Article
    | Open Access

    Stochastic fluctuations at the transcriptional level contribute to heterogeneity in isogenic cell populations. Here, the authors engineer TuNR which modulates the variability in gene expression of endogenous human genes independent of their mean expression.

    • Alain R. Bonny
    • , João Pedro Fonseca
    •  & Hana El-Samad
  • Article
    | Open Access

    Macrophages can be polarized by in vitro culture stimuli into M1 or M2 cells, but microenvironments in vivo are more complex. Here the authors analyze cultured macrophages stimulated with a combination of M1 and M2 stimuli by single-cell RNA sequencing, machine learning, and single-cell secretion profiling to show a surprising level of heterogeneity of response.

    • Andrés R. Muñoz-Rojas
    • , Ilana Kelsey
    •  & Kathryn Miller-Jensen
  • Article
    | Open Access

    Here, the authors apply live-cell and in situ fluorescence imaging at the single-molecule level to examine lambda DNA replication in single cells, finding that individual phage DNAs sequester host factors to their own vicinity and confine their replicated DNAs into separate compartments, suggesting that phage decision-making transcripts are spatially organized in separate compartments to allow distinct subcellular decisions to develop.

    • Jimmy T. Trinh
    • , Qiuyan Shao
    •  & Lanying Zeng
  • Article
    | Open Access

    Cellular signalling networks provide information to the cell, but the trade-off between accuracy of information transfer and energetic cost of doing so has not been assessed. Here, the authors investigate a MAPK signalling cascade in budding yeast and find that information is maximised per unit energetic cost.

    • Alexander Anders
    • , Bhaswar Ghosh
    •  & Victor Sourjik
  • Article
    | Open Access

    Cell fate commitment is understood in terms of bistable regulatory circuits with hysteresis, but inherent stochasticity in gene expression is incompatible with hysteresis. Here, the authors quantify how, under slow dynamics, the dependency of the non-stationary solutions on the initial state of the cells can lead to transient hysteresis.

    • M. Pájaro
    • , I. Otero-Muras
    •  & A. A. Alonso
  • Article
    | Open Access

    Quantifying the effects of noise in gene expression is difficult since noise and mean expression are coupled. Here the authors determine fitness landscapes in mean-noise expression space to uncouple these two parameters and show that changes in noise and mean expression are similarly detrimental to fitness.

    • Jörn M. Schmiedel
    • , Lucas B. Carey
    •  & Ben Lehner
  • Article
    | Open Access

    We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter cell cycle duration are driven by asymmetric divisions.

    • Ulrich Berge
    • , Daria Bochenek
    •  & Ruth Kroschewski
  • Article
    | Open Access

    Phenotypic cell-to-cell variability contributes to fractional killing, but the mechanisms are incompletely understood. Here the authors show that mitochondrial density correlates with cell survival in response to TRAIL, and that variable effective concentrations of Bax/Bak contribute to the effect.

    • Luís C. Santos
    • , Robert Vogel
    •  & Pablo Meyer
  • Article
    | Open Access

    How cellular noise impacts metabolic trade-offs remains unknown. Here, the authors use a quantitative single-cell mass imaging strategy to reveal that cellular noise impacts cellular biomass and triacylglycerol accumulation, as well as protein and fatty-acid recycling under starvation, differently.

    • A. E. Vasdekis
    • , H. Alanazi
    •  & G. Stephanopoulos
  • Article
    | Open Access

    The same protein abundance can be achieved by many combinations of transcription, translation and degradation rates. Here, the authors find that genes combining high transcription with low translation rate are rare due to a trade-off between the cost of transcription and expression noise.

    • Jean Hausser
    • , Avi Mayo
    •  & Uri Alon
  • Article
    | Open Access

    Noisy gene expression leading to phenotypic variability can help organisms to survive in changing environments. Here, Patange et al. show that noisy expression of a stress response regulator, RpoS, allows E. coli cells to modulate their growth rates to survive future adverse environments.

    • Om Patange
    • , Christian Schwall
    •  & James C. W. Locke
  • Article
    | Open Access

    The drivers of growth rate variability in bacteria are yet unknown. Here, the authors present a theory to predict the growth dynamics of individual cells and use a stochastic cell model integrating metabolism, gene expression and replication to identify the processes that underlie growth variation.

    • Philipp Thomas
    • , Guillaume Terradot
    •  & Andrea Y. Weiße
  • Article
    | Open Access

    The intractability of most stochastic models of gene regulatory networks (GRNs) limits their utility. Here, the authors present a linear-mapping approximation mapping models onto simpler ones, giving approximate but accurate analytic or semi- analytic solutions for a wide range of model GRNs.

    • Zhixing Cao
    •  & Ramon Grima
  • Article
    | Open Access

    How bacteria migrate collectively despite individual phenotypic variation is not understood. Here, the authors show that cells spontaneously sort themselves within moving bands such that variations in individual tumble bias, a determinant of gradient climbing speed, are compensated by the local gradient steepness experienced by individuals.

    • X. Fu
    • , S. Kato
    •  & T. Emonet
  • Article
    | Open Access

    While gene expression noise in single-celled organisms is well understood, it is less so in the context of tissues. Here the authors show that coupling between cells in tissues can increase or decrease cell-to-cell variability depending on the level of noise intrinsic to the regulatory networks.

    • Stephen Smith
    •  & Ramon Grima
  • Article
    | Open Access

    A unified framework to understand gene expression noise is still lacking. Here the authors derive a universal theorem relating the biological noise with dynamics of birth and death processes and present a model of transcription dynamics, allowing analytical prediction of the dependence of mRNA noise on mRNA lifetime variability.

    • Seong Jun Park
    • , Sanggeun Song
    •  & Jaeyoung Sung
  • Article
    | Open Access

    Commitment to different fates by differentiating pluripotent cells depends upon integration of external and internal signals. Here the authors analyse the entry of mouse embryonic stem cells into retinoic acid-mediated differentiation using single cell transcriptomics with high temporal resolution.

    • Stefan Semrau
    • , Johanna E. Goldmann
    •  & Alexander van Oudenaarden
  • Article
    | Open Access

    Gene expression is a noisy process, but it is not known how noise in gene expression changes during the aging of single cells. Here the authors show that noise decreases during normal aging, and provide support for aging-associated increases in chromatin state transitions governing noise reduction.

    • Ping Liu
    • , Ruijie Song
    •  & Murat Acar
  • Article
    | Open Access

    Cells must function despite the noisiness of their processes by tolerating or reducing such variability. Here, the authors combine experiment and modelling to show that a network motif that mediates network-dosage compensation also reduces noise in network output, suggesting that noise is tuneable.

    • Weilin Peng
    • , Ruijie Song
    •  & Murat Acar
  • Article
    | Open Access

    TATA boxes in gene promoters are associated with high level of cell-to-cell variation in gene expression. Through integration of multiple data sets, the authors now provide insights into how the interactions of TBP with DNA and other proteins can lead to noisy expression.

    • Charles N. J. Ravarani
    • , Guilhem Chalancon
    •  & M. Madan Babu
  • Article |

    The quantitative relationship between the fluctuation of specific extrinsic and intrinsic factors, and stochastic fluctuations in gene expression - or noise - has not been clearly established. Here, Yang et al.demonstrate that intrinsic noise is independent of - while extrinsic noise scales linearly with - variation in RNA polymerase abundance.

    • Sora Yang
    • , Seunghyeon Kim
    •  & Nam Ki Lee