Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glioblastoma multiforme cancer stem cells from different patients exhibit consistent gene expression and mechanical phenotypes across distinct states in culture

ABSTRACT: Cancer stem cells are responsible for the regenerative properties of tumors, manifested as recurrence and metastasis. They can adopt different states, some of which may not be sensitive to current therapies. Modeling distinct states in culture will contribute towards efficient drug discovery. We previously demonstrated that putative cancer stem cells from multiple glioblastoma patients can be efficiently maintained under different signal transduction states by means of different culture conditions; each state is marked by different levels of STAT3 phosphorylation and Hes3 expression. Here we perform global gene expression and mechanical analyses on three primary cell lines to better characterize each state and to address their broad relevance. We report consistent gene expression profiles and mechanical phenotypes among the three lines across different states. Our data argues for the use of specific culture conditions to model distinct states, all of which may be useful in therapeutic design.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77751 | GEO | 2019/08/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Glioblastoma multiforme cancer stem cells from different patients exhibit consistent gene expression changes following Hes3 RNA interference

Project description:Cancer cells are plastic, switching between signaling pathways to regulate growth under different conditions. In the tumor microenvironment this likely helps them evade therapies that target specific pathways. We must identify all possible signaling states and utilize them in drug screening programs to. One such state is characterized by expression of the transcription factor Hes3 and sensitivity to Hes3 knockdown and can be modeled in vitro by the use of defined culture conditions. Here we modeled this state in vitro, characterized it, and used it to identify drugs that target it. We cultured three primary human brain cancer cell lines, each from a different patient, under three different culture conditions (low, medium, and high Hes3 expression) and characterized gene regulation (RNA sequencing) and mechanical phenotype (real-time deformability assay). We also assessed gene expression regulation following Hes3 knockdown in conditions that maintain high Hes3 expression. We then employed a commonly used human brain tumor cell line to screen 1,600 FDA-approved compounds that specifically target the Hes3-high state in two different culture conditions (high and low Hes3). Cells from multiple patients behave similarly when placed under distinct culture conditions, in the assays described. We identified 37 FDA-approved compounds that specifically kill cancer cells in conditions characterized by high but not those characterized by low Hes3 expression. Our work reveals novel, potentially core signaling states in cancer, a strategy to identify treatments against them, and a set of putative drugs for potential repurposing.

2019-12-31 | GSE120647 | GEO

Glioblastoma multiforme cancer stem cells from different patients exhibit consistent gene expression changes following Hes3 RNA interference

Project description:Glioblastoma multiforme cancer stem cells from different patients exhibit consistent gene expression changes following Hes3 RNA interference

| PRJNA493831 | ENA

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Project description:Impact of static mechanical tension on global gene expressison in dendritic cell culture

2021-11-14 | GSE162061 | GEO

Mechanical confinement governs phenotypic plasticity in melanoma [HMGB2OE_RNAseq]

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

Mechanical confinement governs phenotypic plasticity in melanoma [confined_RNAseq]

2024-01-24 | GSE253800 | GEO

Mechanical confinement governs phenotypic plasticity in melanoma [HMGB2OE_ATACseq]

2024-01-24 | GSE253802 | GEO

Mechanical Compression Creates a Quiescent Muscle Stem Cell Niche

Project description:We discovered mechanical compression is able to bring activated MuSCs back to their quiescent stem cell state.

2022-02-06 | GSE196101 | GEO

Gene expression data from Min6 cells grown in serum containing and serum free condtions following Hes3 knock down

Project description:The basic helix-loop-helix (bHLH) transcription factor hairy and enhancer of split (Hes3) is a member of the Hes/Hey gene family that regulates developmental processes in progenitor cells from various tissues. We demonstrated the Hes3 expression in mouse pancreatic tissue, suggesting it may have a role in modulating beta-cell function. We employed a transfection approach to address specific functions of Hes3. Hes3 RNA interference opposed the growth of the mouse insulinoma cell line Min6. Western blotting and PCR approaches specifically showed that Hes3 RNA interference opposes the expression of Pdx1 and insulin. Likewise, Hes3 knock down reduced evoked insulin release from Min6 cells. We used microarray analysis to examine differences in gene expression when Hes3 expression was knocked down in cells grown under different culture condtions.

2014-12-23 | E-GEOD-64449 | biostudies-arrayexpress

Regional transcriptomics and mechanical properties of rat Achilles tendons

Project description:The transcriptome of different tendons varies based on anatomical location and is likely influenced by the biomechanical loading environment. While differences in biologic and mechanical properties of whole tendons have been assessed, less is understood about differences within a tendon along its proximal-distal axis. Therefore, our objective was to determine the characteristics of and relationship between the transcriptomes and mechanical properties of a single tendon.

2022-11-03 | GSE193408 | GEO

Changes in gene expression after mechanical loading with and without satellite cell.

Project description:Skeletal muscle is a plastic tissue, adapting to different stimuli. Mechanical overload causes muscle hypertrophy and substantial changes in gene expression. We perform a time course analysis following synergistic ablation surgery to induce compensatory hypertrophy in the plantaris muscle in satellite cell depleted mice and wild-type mice. Microarray was used to determine the different expressed genes in skeletal muscle with or without satellite cell following mechanical overload.

2021-07-12 | GSE153542 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data