Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells

ABSTRACT: Cellular phenotypes are dictated not by single signals but by the integration of multiple extracellular cues, a process that remains poorly understood. Here, we systematically dissect how combinations of Oncostatin M, Transforming Growth Factor β1, and Epidermal Growth Factor shape the behavior of MCF10A mammary epithelial cells. Live-cell imaging revealed that ligand combinations drive emergent phenotypes absent in single-ligand contexts, pointing to the induction of novel molecular programs. Transcriptomic profiling uncovered synergistically regulated genes, while partial least-squares regression linked these transcriptional signatures to quantitative imaging-derived phenotypes and validated them across independent datasets. Functional analysis revealed CXCR2 signaling, upregulated through CREB activation, as a key driver of enhanced cell motility under combinatorial ligand treatment. Together, these findings establish a framework for uncovering how extracellular signals converge to modulate gene expression and phenotype, providing new insight into the principles governing complex epithelial cell behaviors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282654 | GEO | 2025/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells

Project description:The local microenvironment plays a critical role in determining cellular phenotype. While responses to many individual ligands have been well characterized, the integration of multiple extracellular signals into a cohesive molecular and phenotypic response remains largely unexplored. Here, we systematically investigate the combinatorial effects of Oncostatin M, Transforming Growth Factor Beta 1, and Epidermal Growth Factor on MCF10A mammary epithelial cells. Live-cell imaging revealed that ligand combinations produce emergent phenotypic responses distinct from single-ligand treatments, suggesting induction of new molecular programs. RNA sequencing showed synergistic upregulation of genes involved in migration and chemotaxis, including CXCL3 and CXCL5. Partial least squares regression identified transcriptional signatures associated with cellular phenotypes quantified from image data, which we validated in independent datasets. Finally, functional analysis revealed that synergistic upregulation of CXCR2 signaling, mediated by CREB activation, contributes to increased cell motility. This study provides a framework for understanding how complex ligand interactions shape phenotypic and molecular landscapes.

2025-08-07 | MSV000098762 | MassIVE

Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells

Project description:Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells

| PRJNA1189550 | ENA

A microfluidics workflow for spatial analysis of microenvironmental gradient impact on cancer cell phenotypes

Project description:Despite the physiological and pathophysiological significance of microenvironmental gradients, tools for generating such gradients and analysing their impact on cellular phenotypes are lacking. Here we present an integrated microfluidics-based workflow for mimicking extracellular pH gradients characteristic of solid tumors, and studying their multifactorial impact on cancer cells. Our microfluidics device generates a pH gradient across cancer cell 3D cultures in an extracellular matrix. The gradient, validated using pH-sensitive fluorophores can be rapidly controlled to represent spatiotemporal microenvironmental changes, and the device allows high resolution live imaging of, e.g., cell motility and chemotaxis. The device can be reopened, allowing immunofluorescence analysis of phenotypes and spatially resolved analysis of gene expression changes across the pH gradient. The workflow is easily adaptable for other gradients and multiple cell types, making it broadly applicable for integrated analysis of roles of microenvironmental gradients in biology.

2024-05-07 | GSE242233 | GEO

Niche-Specific Re-Programming of Epigenetic Landscapes Drives Myeloid Cell Diversity in NASH [scRNA-seq]

Project description:Tissue resident macrophages and recruited monocyte-derived macrophages contribute to host defense but also play pathological roles in a diverse range of human diseases. Multiple macrophage phenotypes are often represented in a diseased tissue, but we lack a deep understanding of the mechanisms that control diversification. Here we use a combination of genetic, genomic, and imaging approaches to investigate the origins and epigenetic trajectories of hepatic myeloid cells during a diet-induced model of nonalcoholic steatohepatitis (NASH). We provide evidence that distinct micro-environments within the NASH liver induce strikingly divergent transcriptomes of resident and infiltrating cells. Myeloid cell diversification results from both remodeling open chromatin landscapes of recruited monocytes and altering activities of pre-existing enhancers of resident Kupffer cells. These findings provide evidence that niche-specific combinations of diseaseassociated environmental signals instruct resident and recruited macrophages to acquire distinct programs of gene expression and corresponding phenotypes.

2020-05-05 | GSE128334 | GEO

Niche-Specific Re-Programming of Epigenetic Landscapes Drives Myeloid Cell Diversity in NASH [RNA-seq]

Project description:Tissue resident macrophages and recruited monocyte-derived macrophages contribute to host defense but also play pathological roles in a diverse range of human diseases. Multiple macrophage phenotypes are often represented in a diseased tissue, but we lack a deep understanding of the mechanisms that control diversification. Here we use a combination of genetic, genomic, and imaging approaches to investigate the origins and epigenetic trajectories of hepatic myeloid cells during a diet-induced model of nonalcoholic steatohepatitis (NASH). We provide evidence that distinct microenvironments within the NASH liver induce strikingly divergent transcriptomes of resident and infiltrating cells. Myeloid cell diversification results from both remodeling open chromatin landscapes of recruited monocytes and altering activities of preexisting enhancers of resident Kupffer cells. These findings provide evidence that niche-specific combinations of disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct programs of gene expression and corresponding phenotypes.

2020-05-10 | GSE128337 | GEO

Niche-Specific Re-Programming of Epigenetic Landscapes Drives Myeloid Cell Diversity in NASH [ChIP-seq]

Project description:Tissue resident macrophages and recruited monocyte-derived macrophages contribute to host defense but also play pathological roles in a diverse range of human diseases. Multiple macrophage phenotypes are often represented in a diseased tissue, but we lack a deep understanding of the mechanisms that control diversification. Here we use a combination of genetic, genomic, and imaging approaches to investigate the origins and epigenetic trajectories of hepatic myeloid cells during a diet-induced model of nonalcoholic steatohepatitis (NASH). We provide evidence that distinct microenvironments within the NASH liver induce strikingly divergent transcriptomes of resident and infiltrating cells. Myeloid cell diversification results from both remodeling open chromatin landscapes of recruited monocytes and altering activities of preexisting enhancers of resident Kupffer cells. These findings provide evidence that niche-specific combinations of disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct programs of gene expression and corresponding phenotypes.

2020-05-05 | GSE128336 | GEO

Niche-Specific Re-Programming of Epigenetic Landscapes Drives Myeloid Cell Diversity in NASH [ATAC-seq]

Project description:Tissue resident macrophages and recruited monocyte-derived macrophages contribute to host defense but also play pathological roles in a diverse range of human diseases. Multiple macrophage phenotypes are often represented in a diseased tissue, but we lack a deep understanding of the mechanisms that control diversification. Here we use a combination of genetic, genomic, and imaging approaches to investigate the origins and epigenetic trajectories of hepatic myeloid cells during a diet-induced model of nonalcoholic steatohepatitis (NASH). We provide evidence that distinct microenvironments within the NASH liver induce strikingly divergent transcriptomes of resident and infiltrating cells. Myeloid cell diversification results from both remodeling open chromatin landscapes of recruited monocytes and altering activities of preexisting enhancers of resident Kupffer cells. These findings provide evidence that niche-specific combinations of disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct programs of gene expression and corresponding phenotypes.

2020-05-05 | GSE128335 | GEO

Comprehensive testing of chemotherapy and immune checkpoint blockade in preclinical cancer models identifies additive combinations

Project description:Background: Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA 4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. Methods: We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. Results: 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8+ T cell activation and upregulation of IFN , TNF and IL-1β signaling. The effective anti tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8+ T cells but was unaffected when TNF or IL 1β cytokine signaling pathways were blocked. Conclusions: Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.

2022-05-02 | GSE188481 | GEO

Circulating microRNAs: Association with lung function in asthma

Project description:Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes. Least squares linear regression was applied with subject phenotypes as the dependent variable, and microRNA Ct values (data matrix quantile normalized) as the independent variable to identify significant associations between subject phenotype and microRNA abundance.

2016-06-09 | E-GEOD-74770 | biostudies-arrayexpress

COMBINE

Project description:Cork Nutrition Cohort

| PRJEB77202 | ENA