Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Escherichia Coli E. Coli
TISSUE(S): Bacterial Cells
SUBMITTER: 
Dhanasekaran Shanmugam
PROVIDER: ST001382 | MetabolomicsWorkbench | Thu May 14 00:00:00 BST 2020
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:In monocytes we used RNA-sequencing to investigate the effect of 4hrs of exposure to buffered hypercapnia (10% CO2) compared to normocapnia (5% CO2) with and without the pro-inflammatory stimulus LPS (2.5ug/ml) for the final 2hrs. Buffered hypercapnia causes transcriptional changes associated with altered metabolic function in both the basal and stimulated states.
2023-04-07 | GSE206333 | GEO
Project description:In wild type, NR4A2-deficient, and NR4A3-deficient monocytes we used RNA-sequencing to investigate the effect of 4hrs of exposure to buffered hypercapnia (10% CO2) compared to normocapnia (5% CO2) with and without the pro-inflammatory stimulus LPS (2.5ug/ml) for the final 2hrs. Buffered hypercapnia causes transcriptional changes associated with altered metabolic function in both the basal and stimulated states.
2024-03-20 | GSE251925 | GEO
Project description:Plasticity enables cells to change their gene expression state in the absence of a genetic change. At the single-cell level, these gene expression states can persist for different lengths of time which is a quantitative measurement referred to as gene expression memory. Because plasticity is not encoded by genetic changes, these cell states can be reversible, and therefore, are amenable to modulation by disrupting gene expression memory. However, we currently do not have robust methods to find the regulators of memory or to track state switching in plastic cell populations. Here, we developed a lineage tracing-based technique to quantify gene expression memory and to identify single cells as they undergo cell state transitions. Applied to human melanoma cells, we quantified long-lived fluctuations in gene expression that underlie resistance to targeted therapy. Further, we identified the PI3K and TGF-β pathways as modulators of these state dynamics. Applying the gene expression signatures derived from this technique, we find that these expression states are generalizable to in vivo models and present in scRNA-seq from patient tumors. Leveraging the PI3K and TGF-β pathways as dials on memory between plastic states, we propose a "pretreatment" model in which we first use a PI3K inhibitor to modulate the expression states of the cell population and then apply targeted therapy. This plasticity informed dosing scheme ultimately yields fewer resistant colonies than targeted therapy alone. Taken together, we describe a technique to find modulators of gene expression memory and then apply this knowledge to alter plastic cell states and their connected cell fates.
2023-09-29 | GSE237228 | GEO
Project description:Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms’ performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light-dependent with a sessile and moddular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled with significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.
2024-01-01 | GSE245487 | GEO
Project description:Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms’ performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light-dependent with a sessile and moddular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled with significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.
2024-01-01 | GSE245492 | GEO
Project description:Cellière2011 - Plasticity of TGF-β Signalling
Transforming growth factor beta (TGF-β) signalling has been implicated as an important regulator of almost all major cell behaviours, including proliferation, differentiation, cell death, and motility. It remains unclear that how the TGF-β signalling pathway accomplishes the flexibility in its responses. What and how many parameters have to be altered for cells to respond differently to perform complex tasks? This canonical response has been explored in this model, by considering the core signalling architecture of TGF-β pathway.
This model is described in the article:
Plasticity of TGF-β signaling
Cellière G, Fengos G, Hervé M, Iber D.
BMC Syst Biol. 2011 Nov 3;5:184.
Abstract:
The family of TGF-β ligands is large and its members are involved in many different signaling processes. These signaling processes strongly differ in type with TGF-β ligands eliciting both sustained or transient responses. Members of the TGF-β family can also act as morphogen and cellular responses would then be expected to provide a direct read-out of the extracellular ligand concentration. A number of different models have been proposed to reconcile these different behaviours. We were interested to define the set of minimal modifications that are required to change the type of signal processing in the TGF-β signaling network.
RESULTS:
To define the key aspects for signaling plasticity we focused on the core of the TGF-β signaling network. With the help of a parameter screen we identified ranges of kinetic parameters and protein concentrations that give rise to transient, sustained, or oscillatory responses to constant stimuli, as well as those parameter ranges that enable a proportional response to time-varying ligand concentrations (as expected in the read-out of morphogens). A combination of a strong negative feedback and fast shuttling to the nucleus biases signaling to a transient rather than a sustained response, while oscillations were obtained if ligand binding to the receptor is weak and the turn-over of the I-Smad is fast. A proportional read-out required inefficient receptor activation in addition to a low affinity of receptor-ligand binding. We find that targeted modification of single parameters suffices to alter the response type. The intensity of a constant signal (i.e. the ligand concentration), on the other hand, affected only the strength but not the type of the response.
CONCLUSIONS:
The architecture of the TGF-β pathway enables the observed signaling plasticity. The observed range of signaling outputs to TGF-β ligand in different cell types and under different conditions can be explained with differences in cellular protein concentrations and with changes in effective rate constants due to cross-talk with other signaling pathways. It will be interesting to uncover the exact cellular differences as well as the details of the cross-talks in future work.
This model is hosted on BioModels Database
and identified by: MODEL1208280000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. PMID: 20587024
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to [CC0 Public Domain Dedication>http://creativecommons.org/publicdomain/zero/1.0/] for more information.
2024-09-02 | BIOMD0000000600 | BioModels
Project description:Metabolic reprogramming has emerged as a crucial regulator of immune cell activation but how systemic metabolism influences immune cell metabolism and function remains to be investigated. To investigate the effect of dyslipidemia on immune cell metabolism, we performed in-depth transcriptional, metabolic and functional characterization of macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage metabolism and attenuate inflammatory macrophage responses. In addition to diminished maximal mitochondrial respiration, hypercholesterolemia reduces the LPS-mediated induction of the pentose phosphate pathway (PPP) and the Nrf2-mediated oxidative stress response. Our observation that suppression of the PPP diminishes LPS-induced cytokine secretion supports the notion that this pathway contributes to inflammatory macrophage responses. Overall, this study reveals that systemic and cellular metabolism are strongly interconnected, together dictating macrophage phenotype and function.
2018-10-31 | GSE107412 | GEO
Project description:Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms’ performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light-dependent with a sessile and moddular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled with significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts. This SuperSeries is composed of the SubSeries listed below.
2024-01-01 | GSE245494 | GEO
Project description:In contrast to the well-established role of oxidative muscle fibers in regulating fatty acid oxidation and whole body metabolism, little is known that about the function of fast/glycolytic muscle fibers in these processes. Here, we generated a skeletal muscle-specific, conditional transgenic mouse expressing a constitutively-active form of Akt1. Transgene activation led to muscle hypertrophy due to the growth of type IIb muscle fibers, which was accompanied by an increase in strength. These mice were then used to assess the consequence of building fast/glycolytic muscle fibers on adiposity and metabolism. Akt1 transgene induction in obese mice resulted in reductions in body weight and fat mass, a resolution of hepatic steatosis and improved metabolic parameters. These effects were achieved independent of changes in physical activity and levels of food consumption. Akt1-mediated skeletal muscle growth opposed the effects of high fat/sucrose diet on transcript expression patterns in the liver, and increased hepatic fatty acid oxidation and ketone body production. Our findings indicate that an increase in fast/glycolytic muscle mass can result in the regression of obesity and obesity-related metabolic disorders in part through its ability to alter fatty acid metabolism in remote tissues. Experiment Overall Design: 11 samples are included in this series. 3 wild-type mice fed on a normal diet, 4 wild-type mice fed on a HF diet, and 4 Akt1 double transgenic mice fed on a HF diet. All samples are on the mixed background.
2008-06-16 | E-GEOD-9484 | biostudies-arrayexpress
Project description:For sessile organisms at high risk from climate change, phenotypic plasticity can be critical to rapid acclimation. Epigenetic markers like DNA methylation are hypothesized as mediators of plasticity; methylation is associated with the regulation of gene expression, can change in response to ecological cues, and is a proposed basis for the inheritance of acquired traits. Within reef-building corals, gene body methylation can change in response to ecological stressors. If coral DNA methylation is transmissible across generations, this could potentially facilitate rapid acclimation to environmental change. We investigated methylation heritability in Acropora, a stony reef-building coral. Two A. millepora and two A. selago adults were crossed, producing eight offspring crosses (four hybrid, two of each species). We used whole-genome bisulfite sequencing to identify methylated loci and allele-specific alignments to quantify per-locus inheritance. If methylation is heritable, differential methylation (DM) between the parents should equal DM between paired offspring alleles at a given locus. We found a mixture of heritable and non-heritable loci, with heritable portions ranging from 44% to 90% among crosses. Gene body methylation was more heritable than intergenic methylation, and most loci had a consistent degree of heritability between crosses (i.e., the deviation between parental and offspring DM were of similar magnitude and direction). Our results provide evidence that coral methylation can be inherited but that heritability is heterogenous throughout the genome. Future investigations into this heterogeneity and its phenotypic implications will be important to understanding the potential capability of intergenerational environmental acclimation in reef building corals."
2024-01-15 | GSE252970 | GEO