An Intrinsic Disordered Region Mediated Confinement State Contributes to Dynamics and Function of Transcription Factors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154771 | GEO | 2021/01/14
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE25440: Individual variation in confinement response at 168h GSE25473: Time course study of confinement stress in HR and LR trout lines Refer to individual Series
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Project description:The effects of short-term confinement on gene expression profiles in blood were evaluated. Fourteen days confinement study was conducted 2 times. In each experiment, 8 male subjects were stayed in an isolation and confinement facility at Japan Aerospace Exploration Agency. DNA microarray of extracted RNA from whole blood samples revealed that the expression levels of 3,659 genes were significantly altered by the 14-day confinement. The changes in gene expression profiles were not exactly the same as those in response to the other stress conditions, such as chronic psychological stress and spaceflight. In particular, 7 genes, LIN9, AK125040.1, MGC45922, C9orf173-AS1, OR1P1P, KRTAP10-12, and ARFRP1, responded to the confinement prominently. Therefore, the analysis of expression levels of these genes might be useful to assess the stress responses of human body to the confinement. In addition, biological interpretation of the alteration of gene expression profiles with Ingenuity Pathway Analysis indicated that 14-day confinement stimulated various signaling related to proinflammation and leukocyte extravasation but suppressed apoptosis signaling. In agreement with the interpretation, the decrease of white blood cells in blood was confirmed during the confinement. On the other hand, red blood cells and platelets did not decrease. These results suggest that 14-day confinement is likely to induce shift of white blood cells from “the circulating pool” to “the marginated pool”.
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Project description:Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such switching is triggered by external cues, the identity of these cues has remained elusive. Here, we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumour cells at the interface between the tumour and surrounding microenvironment. Morphological analysis of these rare cells showed flattened, elliptical nuclei suggestive of mechanical confinement by nearby adjacent tissue. Spatial and single-cell transcriptomics demonstrated that the interface cells adopted a gene program of neuronal invasion, including acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favour the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2high tumour cells are less proliferative but more drug resistant. Our results implicate the mechanical microenvironment as a mechanism for phenotype switching in melanoma.
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Project description:Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such switching is triggered by external cues, the identity of these cues has remained elusive. Here, we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumour cells at the interface between the tumour and surrounding microenvironment. Morphological analysis of these rare cells showed flattened, elliptical nuclei suggestive of mechanical confinement by nearby adjacent tissue. Spatial and single-cell transcriptomics demonstrated that the interface cells adopted a gene program of neuronal invasion, including acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favour the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2high tumour cells are less proliferative but more drug resistant. Our results implicate the mechanical microenvironment as a mechanism for phenotype switching in melanoma.
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Project description:Farmed fish are unavoidably exposed to husbandry-related stressors which can result in outbreaks of disease, reduced reproductive success and poor growth. Biomarkers are needed for the establishment of selective breeding approaches for the production of stress resistant fish. In this context, microarray analysis has been carried out on liver tissues of two genetic lines of rainbow trout, high responders (HR) and low responders (LR), after confinement for various time periods. Microarray hybridisations provided gene expression profiles for pools of fish (stress: n=5; control: n=3) after 6h, 24h and 168h of confinement stress. Keywords : stress response, pools, time course, comparison of two lines. Samples were hybridised directly to each other in a parallel loop design. Each treatment (LC, LS, HC, HS) was hybidised in a loop of all 3 time points and each treatment loop was interconnected by hybridisations at a specific time. The publication will have this figure.
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Project description:Farmed fish are unavoidably exposed to husbandry-related stressors which can result in outbreaks of disease, reduced reproductive success and poor growth. Biomarkers are needed for the establishment of selective breeding approaches for the production of stress resistant fish. In this context, microarray analysis has been carried out on liver tissues of two genetic lines of rainbow trout, high responders (HR) and low responders (LR), after confinement for various time periods. Microarray hybridisations provided gene expression profiles for pools of fish (stress: n=5; control: n=3) after 6h, 24h and 168h of confinement stress. Keywords : stress response, pools, time course, comparison of two lines.
2010-11-24 | GSE25473 | GEO
Project description:Farmed fish are unavoidably exposed to husbandry-related stressors which can result in outbreaks of disease, reduced reproductive success and poor growth. Biomarkers are needed for the establishment of selective breeding approaches for the production of stress resistant fish. In this context, microarray analysis has been carried out on liver tissues of two genetic lines of rainbow trout, high responders (HR) and low responders (LR), after confinement for various time periods. Microarray hybridisations provided gene expression profiles for 10 individual fish (5 of the HR line and 5 of the LR line) after 168h of confinment stress. Keywords : stress response, individual variation, fixed time point, comparison of two lines All 10 samples were hybridised against a common reference source that contained equal amounts of all 10 samples. Each sample was hybridised twice against this reference using a dye-swap setup.
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