scholarly journals Single-cell heterogeneity in the chloroplast redox state mediates acclimation to stress in a marine diatom

2018 ◽  
Author(s):  
Avia Mizrachi ◽  
Shiri Graff van Creveld ◽  
Orr H. Shapiro ◽  
Shilo Rosenwasser ◽  
Assaf Vardi
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Stress Responses ◽  
Population Level ◽  
Marine Diatom ◽  
Photosynthetic Microorganisms ◽  
Metabolic Heterogeneity ◽  
Cell To Cell Variability ◽  
Level Analysis ◽  
Redox Dynamics

AbstractDiatoms are photosynthetic microorganisms of great ecological and biogeochemical importance, forming vast blooms in diverse aquatic ecosystems. Current understanding of phytoplankton acclimation to stress is based on population-level analysis, masking cell-to-cell variability. Here we investigated heterogeneity within Phaeodactylum tricornutum populations in response to oxidative stress, which is induced by environmental stress conditions. We combined flow cytometry and a microfluidics system for live imaging to measure redox dynamics at the single-cell level using the roGFP sensor. Chloroplast-targeted roGFP exhibited a light-dependent, bi-stable oxidation pattern in response to H2O2, revealing distinct subpopulations of sensitive oxidized cells and resilient reduced cells. Subpopulation proportions depended on growth phase, linking the bi-stable phenotype to proliferation. Oxidation of chloroplast-targeted roGFP preceded commitment to cell death and was used as a novel cell fate predictor. We propose that light-dependent metabolic heterogeneity results in differential stress responses that regulate cell fate within diatom populations.

scholarly journals Light-dependent single-cell heterogeneity in the chloroplast redox state regulates cell fate in a marine diatom

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Avia Mizrachi ◽  
Shiri Graff van Creveld ◽  
Orr H Shapiro ◽  
Shilo Rosenwasser ◽  
Assaf Vardi
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Phaeodactylum Tricornutum ◽  
Marine Diatom ◽  
Redox Sensor ◽  
Fundamental Understanding ◽  
Photosynthetic Microorganisms ◽  
Sense And Respond ◽  
Metabolic Heterogeneity ◽  
Cell To Cell Variability

Diatoms are photosynthetic microorganisms of great ecological and biogeochemical importance, forming vast blooms in aquatic ecosystems. However, we are still lacking fundamental understanding of how individual cells sense and respond to diverse stress conditions, and what acclimation strategies are employed during bloom dynamics. We investigated cellular responses to environmental stress at the single-cell level using the redox sensor roGFP targeted to various organelles in the diatom Phaeodactylum tricornutum. We detected cell-to-cell variability using flow cytometry cell sorting and a microfluidics system for live imaging of oxidation dynamics. Chloroplast-targeted roGFP exhibited a light-dependent, bi-stable oxidation pattern in response to H2O2 and high light, revealing distinct subpopulations of sensitive oxidized cells and resilient reduced cells. Early oxidation in the chloroplast preceded commitment to cell death, and can be used for sensing stress cues and regulating cell fate. We propose that light-dependent metabolic heterogeneity regulates diatoms’ sensitivity to environmental stressors in the ocean.

scholarly journals Expression variation and covariation impair analog and enable binary signaling control

2018 ◽  
Author(s):  
Kyle M. Kovary ◽  
Brooks Taylor ◽  
Michael L. Zhao ◽  
Mary N. Teruel
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Activation ◽  
Signal Transmission ◽  
Population Level ◽  
Stimulus Range ◽  
Level Control ◽  
Cell Fate Decisions ◽  
Cell Functions ◽  
Cell To Cell Variability

AbstractDue to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (CV) of approximately 25% between cells. This high variation enables population-level regulation of cell functions but abolishes accurate single-cell signal transmission. Here we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual Xenopus laevis eggs and cultured human cells and show that variation is typically much lower, in the range of 5–15%, compatible with accurate single-cell transmission. Furthermore, we show that MEK and ERK expression covary which improves controllability of the fraction of cells that activate bimodal ERK signaling, arguing that covariation has a role in facilitating population-level control of binary cell-fate decisions. Together, our experimental and model data argues for a control principle whereby low covariation limits signaling noise for accurate control analog single-cell signaling. In contrast, increased covariation widens the stimulus-range over which external inputs can regulate binary cell activation, thereby enabling accurate control of the fraction of activated cells at the population level.

Pulses and delays, anticipation and memory: seeing bacterial stress responses from a single-cell perspective

2020 ◽  
Vol 44 (5) ◽  
pp. 565-571
Author(s):  
Valentine Lagage ◽  
Stephan Uphoff
Keyword(s):  
Stress Response ◽  
Single Cell ◽  
Single Molecule ◽  
Stress Responses ◽  
Phenotypic Diversity ◽  
Single Cells ◽  
Super Resolution ◽  
Population Level ◽  
Protective Mechanisms ◽  
Single Cell Imaging

ABSTRACT Stress responses are crucial for bacteria to survive harmful conditions that they encounter in the environment. Although gene regulatory mechanisms underlying stress responses in bacteria have been thoroughly characterised for decades, recent advances in imaging technologies helped to uncover previously hidden dynamics and heterogeneity that become visible at the single-cell level. Despite the diversity of stress response mechanisms, certain dynamic regulatory features are frequently seen in single cells, such as pulses, delays, stress anticipation and memory effects. Often, these dynamics are highly variable across cells. While any individual cell may not achieve an optimal stress response, phenotypic diversity can provide a benefit at the population level. In this review, we highlight microscopy studies that offer novel insights into how bacteria sense stress, regulate protective mechanisms, cope with response delays and prepare for future environmental challenges. These studies showcase developments in the single-cell imaging toolbox including gene expression reporters, FRET, super-resolution microscopy and single-molecule tracking, as well as microfluidic techniques to manipulate cells and create defined stress conditions.

scholarly journals Cell-to-cell heterogeneity in p38-mediated cross-inhibition of JNK causes stochastic cell death

2017 ◽  
Author(s):  
Haruko Miura ◽  
Yohei Kondo ◽  
Michiyuki Matsuda ◽  
Kazuhiro Aoki
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Stress Responses ◽  
Imaging System ◽  
Single Cells ◽  
High Specificity ◽  
Cellular Heterogeneity ◽  
Cell Fate Decisions ◽  
Specificity And Sensitivity ◽  
Cross Inhibition

AbstractThe stress activated protein kinases (SAPKs), c-Jun N-terminal kinase (JNK) and p38, are important players in cell fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in the inflammatory and stress responses. However, it is still unknown how this crosstalk affects signaling dynamics, cell-to-cell variation, and cellular responses at the single-cell level. To address these questions, we established a multiplexed live-cell imaging system based on kinase translocation reporters to simultaneously monitor JNK and p38 activities with high specificity and sensitivity at single-cell resolution. Various stresses, such as anisomycin, osmotic stress, and UV irradiation, and pro-inflammatory cytokines activated JNK and p38 with various dynamics. In all cases, however, p38 suppressed JNK activity in a cross-inhibitory manner. We demonstrate that p38 antagonizes JNK through both transcriptional and post-translational mechanisms. This cross-inhibition of JNK appears to generate cellular heterogeneity in JNK activity after stress exposure. Our data indicate that this heterogeneity in JNK activity plays a role in fractional killing in response to UV stress. Our highly sensitive multiplexed imaging system enables detailed investigation into the p38-JNK interplay in single cells.One Sentence SummaryCross-inhibition by p38 generates cell-to-cell variability in JNK activity.

scholarly journals Analysis of cell size homeostasis at the single-cell and population level

2018 ◽  
Author(s):  
Philipp Thomas
Keyword(s):  
Single Cell ◽  
Cell Size ◽  
Single Cells ◽  
Population Level ◽  
Power Laws ◽  
Size Distributions ◽  
Unified Framework ◽  
Lineage Tree ◽  
Cell To Cell Variability ◽  
Cell Data

Growth pervades all areas of life from single cells to cell populations to tissues. However, cell size often fluctuates significantly from cell to cell and from generation to generation. Here we present a unified framework to predict the statistics of cell size variations within a lineage tree of a proliferating population. We analytically characterise (i) the distributions of cell size snapshots, (ii) the distribution within a population tree, and (iii) the distribution of lineages across the tree. Surprisingly, these size distributions differ significantly from observing single cells in isolation. In populations, cells seemingly grow to different sizes, typically exhibit less cell-to-cell variability and often display qualitatively different sensitivities to cell cycle noise and division errors. We demonstrate the key findings using recent single-cell data and elaborate on the implications for the ability of cells to maintain a narrow size distribution and the emergence of different power laws in these distributions.

scholarly journals Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes define survival threshold in erythroid progenitor cells

2019 ◽  
Author(s):  
Lorenz Adlung ◽  
Paul Stapor ◽  
Christian Tönsing ◽  
Leonard Schmiester ◽  
Luisa E. Schwarzmüller ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Cell Population ◽  
Population Level ◽  
Minimal Amount ◽  
List Type ◽  
Erythroid Progenitor ◽  
Binary Decision ◽  
Erythroid Progenitor Cells ◽  
Cell To Cell Variability

SummarySurvival or apoptosis is a binary decision in individual cells. Yet, at the cell population level, a graded increase in survival of CFU-E cells is observed upon stimulation with Erythropoietin (Epo). To identify components of JAK2/STAT5 signal transduction that contribute to the graded population response, a cell population-level model calibrated with experimental data was extended to study the behavior in single cells. The single-cell model showed that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of EpoR:JAK2 complexes and of SHP1 as well as the extent of nuclear import due to the large variance in the cytoplasmic volume of CFU-E cells. 24 to 118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes are responsible to convert a switch-like behavior at the single-cell level to a graded population level response.HighlightsMathematical modeling enables integration of heterogeneous dataSingle-cell modeling captures binary decision processMultiple sources of cell-to-cell variability in erythroid progenitor cellsMinimal amount of active STAT5 sufficient for survival of erythroid progenitor cells

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