Mechanical confinement governs phenotypic plasticity in melanoma [HMGB2OE_ATACseq]
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PROVIDER: PRJNA1067149 | ENA |
REPOSITORIES: ENA
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Project description:Mechanical confinement governs phenotypic plasticity in melanoma
| PRJNA1067145 | ENA
Project description:Mechanical confinement governs phenotypic plasticity in melanoma [HMGB2OE_RNAseq]
| PRJNA1067146 | ENA
Project description:Mechanical confinement governs phenotypic plasticity in melanoma [confined_RNAseq]
| PRJNA1067147 | ENA
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.
2024-01-24 | GSE253802 | GEO
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.
2024-01-24 | GSE253801 | GEO
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.
2024-01-24 | GSE253800 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-24 | GSE253803 | GEO
Project description:Mechanical stress can modulate the fate of cells in both physiological and extreme conditions. Recurrence of tumors after thermal ablation, a radical therapy for many cancers, indicates that some tumor cells can endure temperatures far beyond physiological ones. This unusual heat resistance with unknown mechanisms remains a key obstacle to fully realizing the clinical potential of thermal ablation. By developing a 3D bioprinting-based thermal ablation system, we demonstrate that hepatocellular carcinoma (HCC) cells in this 3D model exhibit enhanced heat resistance as compared with cells on plates. Mechanistically, the activation of transcription factor SP1 under mechanical confinement enhances the transcription of Interleukin-4-Induced-1, which catalyzes tryptophan metabolites to activate the aryl hydrocarbon receptor (AHR), leading to heat resistance. Encouragingly, the AHR inhibitor prevents HCC recurrence after thermal ablation. These findings reveal a previously unknown role of mechanical confinement in heat resistance and provide a rationale for AHR inhibitors as neoadjuvant therapy.
2023-06-25 | GSE235351 | GEO
Project description:Phenotypic Plasticity upon GSC Differentiation
| PRJNA1065463 | ENA
Project description:Traditionally, the study of evolution has focused on heritable variation, because selection on non-heritable phenotypic variation was deemed non-important for its inability to cause evolutionary responses such as diversification of lineages. Recently however, it has been suggested that also environmentally induced phenotypic variation such as phenotypic plasticity can play an important role in adaptive responses resulting in diversification. The purpose of this study is to investigate the importance of phenotypic plasticity for the diversification of lineages, using life history, morphological traits, and genomic profiling during post embryonic development in plastic and non-plastic genotypes of the common frog Rana temporaria. Six animals each originating from four different islands were reared in either constant or reduced water conditions and hepatic mRNA levels of Gosner stage 37 animals evaluated by MAGEX DNA array analysis.
2014-03-18 | E-GEOD-42274 | biostudies-arrayexpress