Featured
-
-
Article
| Open AccessFitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Generating and controlling cell collective behavior is important for synthetic biology and bioproduction. Here, the authors show the diversification dynamic and the fitness cost associated with cell switching are coupled in yeast and bacteria, and demonstrate the feasibility of controlling diversification regimes.
- Lucas Henrion
- , Juan Andres Martinez
- & Frank Delvigne
-
Article
| Open AccessDynamic fluctuations in a bacterial metabolic network
The interconnected network of cellular metabolism is potentially prone to generating oscillatory behaviour. Here, the authors use single-cell FRET measurements of pyruvate levels to reveal large periodic fluctuations in bacterial glycolysis.
- Shuangyu Bi
- , Manika Kargeti
- & Victor Sourjik
-
Article
| Open AccessIndependent control of mean and noise by convolution of gene expression distributions
Gene expression noise can reduce fitness but analysis is hampered by a scaling relationship between noise and expression level. Here the authors show that gene expression mean and noise can be independently controlled by expressing two copies of a gene from separate inducible promoters in the same cell.
- Karl P. Gerhardt
- , Satyajit D. Rao
- & Jeffrey J. Tabor
-
Article
| Open AccessIntrons control stochastic allele expression bias
Stochastic autosomal allele expression bias has been widely documented, yet the mechanisms behind this consequential phenomenon remain poorly understood. Here the authors show that the presence of introns greatly restricts monoallelic expression in a C. elegans model.
- Bryan Sands
- , Soo Yun
- & Alexander R. Mendenhall
-
Article
| Open AccessStochastic pausing at latent HIV-1 promoters generates transcriptional bursting
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 AccessPareto optimality between growth-rate and lag-time couples metabolic noise to phenotypic heterogeneity in Escherichia coli
It is unclear how noise in gene expression propagates to phenotypic heterogeneity in clonal bacterial populations. Here, the authors explore how variability in central sugar metabolism in E. coli can mediate and promote population diversification.
- Diego Antonio Fernandez Fuentes
- , Pablo Manfredi
- & Mattia Zampieri
-
Article
| Open AccessOrthogonal control of mean and variability of endogenous genes in a human cell line
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 AccessCo-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells
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 AccessEmerging heterogeneous compartments by viruses in single bacterial cells
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 AccessDesign of a MAPK signalling cascade balances energetic cost versus accuracy of information transmission
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 AccessTransient hysteresis and inherent stochasticity in gene regulatory networks
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 AccessDissecting splicing decisions and cell-to-cell variability with designed sequence libraries
Alternative splicing is regulated by multiple mechanisms. Here the authors employed designed splice site libraries and massively parallel reporter assays to dissect the regulatory complexity and cell-to-cell variability of splicing decisions and to build accurate predictive models.
- Martin Mikl
- , Amit Hamburg
- & Eran Segal
-
Article
| Open AccessEmpirical mean-noise fitness landscapes reveal the fitness impact of gene expression noise
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 AccessFeed-forward regulation adaptively evolves via dynamics rather than topology when there is intrinsic noise
Feed‐forward loops (FFLs) can filter out noise, but whether their overrepresentation in GRNs reflects adaptive evolution for this function is debated. Here, the authors develop a null model of regulatory evolution and find that FFLs evolve readily under selection for the noise filtering function.
- Kun Xiong
- , Alex K. Lancaster
- & Joanna Masel
-
Article
| Open AccessAsymmetric division events promote variability in cell cycle duration in animal cells and Escherichia coli
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 AccessMitochondrial origins of fractional control in regulated cell death
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 AccessEliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging
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 AccessCentral dogma rates and the trade-off between precision and economy in gene expression
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 AccessEscherichia coli can survive stress by noisy growth modulation
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 AccessSources, propagation and consequences of stochasticity in cellular growth
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 AccessPulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation
Natural transcription factors are often regulated in a pulsatile fashion unlike many synthetic systems. Here the authors show that dynamic pulsatile signals reduce cell-to-cell gene expression variability in an optogenetic construct.
- Dirk Benzinger
- & Mustafa Khammash
-
Article
| Open AccessLinear mapping approximation of gene regulatory networks with stochastic dynamics
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 AccessSpatial self-organization resolves conflicts between individuality and collective migration
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 AccessMitochondrial levels determine variability in cell death by modulating apoptotic gene expression
It is unclear what causes variation in cell death in response to chemotherapy. Here, the authors show that cellular mitochondrial content modulates apoptotic protein levels, which in turn regulates response to agents such as TRAIL.
- Silvia Márquez-Jurado
- , Juan Díaz-Colunga
- & Francisco J. Iborra
-
Article
| Open AccessSingle-cell variability in multicellular organisms
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 AccessThe Chemical Fluctuation Theorem governing gene expression
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 AccessDynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells
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 AccessNoise reduction as an emergent property of single-cell aging
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 AccessMicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord
In the spinal cord, someHox genes are transcribed in progenitors while their proteins are only detected in differentiating postmitotic motor neurons. Here, the authors show that miRNAs (specifically mir-27) regulate post-transcriptional Hoxa5 expression in motor neurons.
- Chung-Jung Li
- , Tian Hong
- & Jun-An Chen
-
Article
| Open AccessNoise reduction facilitated by dosage compensation in gene networks
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 AccessAffinity and competition for TBP are molecular determinants of gene expression noise
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 |
Contribution of RNA polymerase concentration variation to protein expression noise
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