Epigenome analysis of lung adenocarcinoma cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63940 | GEO | 2014/12/08
SECONDARY ACCESSION(S): PRJNA269569
REPOSITORIES: GEO
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Project description:An integrated approach combining genomics, proteomics and DNA methylation with functional profiling to define molecular features associated with epithelial to mesenchymal transition (EMT) states. Genomic DNA from 36 lung adenocarcinoma cell lines was bisulfite treated and analyzed on the Illumina Infinium HumanMethylation27K BeadChip
2014-12-08 | E-GEOD-63940 | biostudies-arrayexpress
Project description:An integrated approach combining genomics, proteomics, DNA methylation and microRNA analysis with functional profiling to define molecular features associated with epithelial to mesenchymal transition (EMT) states.
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Project description:This model is an expansion of the Regan2022 - Mechanosensitive EMT model (MODEL2208050001); it includes a TGFβ signaling module and autocrine signaling in mesenchymal cells. The expanded 150-node (630 link) modular model undergoes EMT triggered by biomechanical and growth signaling crosstalk, or by TGFβ. As its predecessor, this model also reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density. In contrast, potent autocrine signaling can stabilize the mesenchymal state in all but very dense monolayers on soft ECM. This expanded model also reproduces the inhibitory effects of TGFβ on proliferation and anoikis resistance in mesenchymal cells, as well as its ability to trigger apoptosis on soft ECM vs. EMT on stiff matrices. The model offers several experimentally testable predictions related to the effect of neighbors on partial vs. full EMT, the tug of war between mitosis and the maintenance of migratory hybrid E/M states, as well as cell cycle defects in dynamic, heterogeneous populations of epithelial, hybrid E/M and mesenchymal cells.
2023-12-13 | MODEL2208050002 | BioModels
Project description:This file contains a 136-node modular Boolean network model of EMT triggered by biomechanical and growth signaling crosstalk, linked to a published network of epithelial contact inhibition, proliferation, and apoptosis (MODEL2006170001). This model reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density.
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Project description:Epithelial-mesenchymal transition (EMT) is a key cellular process involved in development and disease progression. Single-cell transcriptomes can reveal intermediate EMT states observed in tumors, but previous studies focused on time-dependent responses in epithelial cells after stimulation with EMT signals as an in vitro model for understanding EMT progression, so it was unclear how transcriptomes can change in response to different levels of EMT inducer. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with various concentrations of TGF-β. We found that the dose-dependent EMT harbors multiple intermediate states at the single-cell level after two weeks of treatment, suggesting a stable EMT continuum. After correcting batch effects from experiments, we performed comparative analyses of the dose- and time-dependent EMT. We found that the dose-dependent EMT shows a stronger anti-correlation between epithelial and mesenchymal transcriptional programs and a better resolution of stages of EMT compared to the time-dependent progress. These properties enable more power to detect genes whose expressions are associated with EMT. Nonetheless, our analyses showed cell clusters unique to the time-dependent EMT, which correspond to en route cell populations that do not appear at steady states. Furthermore, combining dose- and time-dependent cell clusters gave rise to more accurate prognosis for cancer patients compared to individual EMT spectrum.
2022-09-20 | GSE213753 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is a key cellular process involved in development and disease progression. Single-cell transcriptomes can reveal intermediate EMT states observed in tumors, but previous studies focused on time-dependent responses in epithelial cells after stimulation with EMT signals as an in vitro model for understanding EMT progression, so it was unclear how transcriptomes can change in response to different levels of EMT inducer. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with various concentrations of TGF-β. We found that the dose-dependent EMT harbors multiple intermediate states at the single-cell level after two weeks of treatment, suggesting a stable EMT continuum. After correcting batch effects from experiments, we performed comparative analyses of the dose- and time-dependent EMT. We found that the dose-dependent EMT shows a stronger anti-correlation between epithelial and mesenchymal transcriptional programs and a better resolution of stages of EMT compared to the time-dependent progress. These properties enable more power to detect genes whose expressions are associated with EMT. Nonetheless, our analyses showed cell clusters unique to the time-dependent EMT, which correspond to en route cell populations that do not appear at steady states. Furthermore, combining dose- and time-dependent cell clusters gave rise to more accurate prognosis for cancer patients compared to individual EMT spectrum.
2022-08-29 | GSE200941 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased quantitative proteomics approach, we found that the morphology of the organoids could predict EMT state, with solid organoids associated with a C-EMT signature. We also observed that exogenous TGFb1 could induce a solid organoid morphology that was associated with changes in the S100 family of proteins and the formation of high-grade tumors. Our work reveals that S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome.
2023-02-24 | PXD030992 | Pride
Project description:Epithelial to Mesenchymal Transition (EMT) renders epithelial cells to acquire migratory characteristics during development and cancer metastasis. While epigenetic and splicing changes have been implicated in EMT, the mechanisms governing their crosstalk remain poorly understood. Here, we identify C2H2 zinc finger protein, ZNF827, a novel factor, is strongly induced during important EMT mediated processes including in brain development and breast cancer metastasis and is required for the molecular and phenotypic changes underlying EMT in these processes. Mechanistically, ZNF827 mediated these responses by orchestrating a large-scale remodeling of the splicing landscape by recruiting HDAC1 for epigenetic modulation of distinct genomic loci, thereby slowing RNA Pol II progression and altering the splicing of transcripts encoding key EMT regulators in cis. These findings reveal an unprecedented complexity between epigenetic landscape and splicing and identifies ZNF827 as a master regulator coupling these processes during EMT in brain development and breast cancer metastasis.
2022-06-21 | PXD034511 | Pride
Project description:Epithelial to Mesenchymal Transition (EMT) has been associated with cancer cell heterogeneity, plasticity and metastasis. It has been the subject of several modeling effort. This logical model of the EMT cellular network aims to assess microenvironmental signals controlling cancer-associated phenotypes amid the EMT continuum. Its outcomes relate to the qualitative degrees of cell adhesions by adherent junctions and focal adhesions, two features affected during EMT. Model attractors recover epithelial, mesenchymal and hybrid phenotypes, and simulations show that hybrid phenotypes may arise through independent molecular paths, involving stringent extrinsic signals.
Of particular interest, model predictions and their experimental validations indicated that: 1) ECM stiffening is a prerequisite for cells overactivating FAK-SRC to upregulate SNAIL1 and acquire a mesenchymal phenotype, and 2) FAK-SRC inhibition of cell-cell contacts through the Receptor Protein Tyrosine Phosphates kappa leads to the acquisition of a full mesenchymal rather than a hybrid phenotype.
2020-06-30 | MODEL2004040001 | BioModels
Project description:Background The plasticity along the epithelial-mesenchymal transition (EMT) spectrum has been shown to be regulated by various epigenetic repertoires. Emerging evidence of local chromatin conformation changes suggests that regulation of EMT may occur at a higher order of three-dimensional genome level. Results We perform Hi-C analysis and combine ChIP-seq data across cancer cell lines representing different EMT states. We demonstrate that the epithelial and mesenchymal genes are regulated distinctively. We find that EMT genes are regulated within their topologically associated domains (TADs), with only a subset of mesenchymal genes being influenced by A/B compartment switches, indicating topological remodelling is required in the transcriptional regulation of these genes. At the TAD level, epithelial and mesenchymal genes are associated with different regulatory trajectories. The epithelial gene-residing TADs are enriched with H3K27me3 marks in the mesenchymal-like states. The mesenchymal gene-residing TADs , which do not show enrichment of H3K27me3 in epithelial-like states, exhibit increased interaction frequencies with regulatory elements in the mesenchymal-like states. Conclusions We propose a novel workflow coupling immunofluorescence and dielectrophoresis to unravel EMT heterogeneity at single-cell resolution. The predicted three-dimensional structures of chromosome 10, harboring Vimentin, identify cell clusters of different states. Our results pioneer a novel avenue to decipher the complexities underlying the regulation of EMT and may infer the barriers of plasticity in the 3D genome context.
2022-05-08 | GSE201917 | GEO