Ontology highlight
ABSTRACT:
PROVIDER: PRJNA724887 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Phytochrome-based extracellular matrix with reversibly tunable mechanical properties
| PRJNA515303 | ENA
Project description:The extracellular matrix (ECM)-regulated phenotypic plasticity is crucial for metastatic progression of triple negative breast cancer (TNBC). To investigate the effect of matrix cues on phenotypic plasticity, we embedded triple negative DU4475 cells from suspension culture into mechanically tunable fibrin gels or basement membrane extract (Matrigel). Cells in suspension culture and matrix cultures showed divergent gene expression profiles, with specific gene expression signatures depending on the biochemical composition and stiffness of the matrix.
2023-04-05 | GSE228939 | GEO
Project description:Adipose stromal cells (ASCs) are the primary source of local estrogens in adipose tissue, aberrant production of which promotes estrogen receptor-positive (ER+) breast cancer. Here we show that extracellular matrix (ECM) rigidity and cell contractility are two opposing determinants for estrogen output of ASCs. Using synthetic ECMs and elastomeric micropost arrays with tunable rigidity, we find that increasing matrix compliance induces transcription of aromatase, a rate-limiting enzyme in estrogen biosynthesis. This mechanical cue is transduced sequentially by Discoidin Domain Receptor 1 (DDR1), c-Jun N-terminal kinase 1 (JNK1), and phosphorylated JunB, which binds to and activates two breast cancer-associated aromatase promoters. In contrast, elevated cell contractility due to actin stress fiber formation dampens aromatase transcription. Mechanically stimulated stromal estrogen production enhances estrogen-dependent transcription in ER+ tumor cells and promotes their growth. This novel mechanotransduction pathway underlies communications between ECM, stromal hormone output, and cancer cell growth within the same microenvironment. Total RNA was isolated from primary adipose stromal cells after 2d culture or 3d Collagen gel for 21 hours. Triplicates for each conditioned were analyzed
2013-03-04 | E-GEOD-44811 | biostudies-arrayexpress
Project description:This dataset is part of a study that aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. This specific dataset includes scRNA-seq and snRNA-seq data from trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) together with EVT differentiation media. This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. Data for primary trophoblast organoids is available under E-MTAB-12650.
| EGAD00001010017 | EGA
Project description:Abstract Objective: To investigate the physiology of ectopic pregnancy by analyzing the miRNA profiles of the pregnancy tissue from both ectopic and control pregnancies (voluntary termination of pregnancy). Design: Research study. Setting: Academic research institute in collaboration with a university hospital. Patients: Patients suffering from tubal EP and patients with a normal ongoing pregnancy scheduled for a voluntary termination of pregnancy (VTOP) were recruited. Interventions: Pregnancy tissue samples were analyzed by miRNA microarray and further validated by qPCR. Main Outcome measures: Gene expression profiles and quantitative PCR measurements. Results: Four miRNAs were found to be downregulated in EP compared to healthy trophoblast tissue, and three miRNAs were upregulated in EP trophoblast compared to control tissue samples. All genes were validated by q-PCR. We found three statistically significant miRNAs, all of which were upregulated in the EP sample group. Conclusion: We describe the alteration of seven miRNAs in EP samples that could alter pathways which are critical for correct implantation such as extracellular matrix (ECM) remodeling, or mucin biosynthesis, thus resulting in ectopic pregnancies.
2014-06-02 | GSE44731 | GEO
Project description:In this study, we investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming, and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC-sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on matrices at 20 kPa, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the co-transporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into the nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. These findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.
2023-12-19 | GSE250066 | GEO
Project description:In this study we report the establishment and characterization of a three-dimensional in vitro, coculture engineered prostate cancer tissue (EPCaT) disease model based upon and informed by our characterization of in vivo prostate cancer (PCa) xenograft tumor stiffness. In prostate cancer, tissue stiffness is known to impact changes in gene and protein expression, alter therapeutic response, and be positively correlated with an aggressive clinical presentation. To inform an appropriate stiffness range for our in vitro model, PC-3 prostate tumor xenografts were established. Tissue stiffness ranged from 95 to 6,750 Pa. Notably, xenograft cell seeding density significantly impacted tumor stiffness; a two-fold increase in the number of seeded cells not only widened the tissue stiffness range throughout the tumor, but also resulted in significant spatial heterogeneity. To fabricate our in vitro EPCaT model, PC-3 castration-resistant prostate cancer cells were co-encapsulated with BJ-5ta fibroblasts within a poly(ethylene glycol)-fibrinogen matrix augmented with excess poly(ethylene glycol)-diacrylate to modulate the matrix mechanical properties. Encapsulated cells temporally remodeled their in vitro microenvironment and enrichment of gene sets associated with tumorigenic progression was observed in response to increased matrix stiffness. Through variation of matrix composition and culture duration, EPCaTs were tuned to mimic the wide range of biomechanical cues provided to PCa cells in vivo; collectively, a range of 50 to 10,000 Pa was achievable. Markedly, this also encompasses published clinical PCa stiffness data. Overall, this study serves to introduce our bioinspired, tunable EPCaT model and provide the foundation for future PCa progression and drug development studies.
2022-05-24 | GSE203495 | GEO
Project description:Abstract Objective: To investigate the physiology of ectopic pregnancy by analyzing the miRNA profiles of the pregnancy tissue from both ectopic and control pregnancies (voluntary termination of pregnancy). Design: Research study. Setting: Academic research institute in collaboration with a university hospital. Patients: Patients suffering from tubal EP and patients with a normal ongoing pregnancy scheduled for a voluntary termination of pregnancy (VTOP) were recruited. Interventions: Pregnancy tissue samples were analyzed by miRNA microarray and further validated by qPCR. Main Outcome measures: Gene expression profiles and quantitative PCR measurements. Results: Four miRNAs were found to be downregulated in EP compared to healthy trophoblast tissue, and three miRNAs were upregulated in EP trophoblast compared to control tissue samples. All genes were validated by q-PCR. We found three statistically significant miRNAs, all of which were upregulated in the EP sample group. Conclusion: We describe the alteration of seven miRNAs in EP samples that could alter pathways which are critical for correct implantation such as extracellular matrix (ECM) remodeling, or mucin biosynthesis, thus resulting in ectopic pregnancies. This study was authorized by the Institutional Review Board/Independent Ethics Committee of the Hospital Universitario La Fe, Valencia, Spain. Eight patients suffering from tubal EP and another eight patients with a normal ongoing pregnancy scheduled for a VTOP were recruited.
2014-06-02 | E-GEOD-44731 | biostudies-arrayexpress
Project description:Increased extracellular matrix (ECM) stiffness has been implicated in esophageal adenocarcinoma (EAC) progression, metastasis, and resistance to therapy. However, the underlying pro-tumorigenic pathways are yet to be defined. Additional work is needed to develop physiologically relevant in vitro 3D culture models that better recapitulate the human tumor microenvironment and can be used to dissect the contributions of matrix stiffness to EAC pathogenesis. Here, we describe a modular, tumor ECM-mimetic hydrogel platform with tunable mechanical properties, defined presentation of cell-adhesive ligands, and protease-dependent degradation that supports robust in vitro growth and expansion of patient-derived EAC 3D organoids (EAC PDOs). Hydrogel mechanical properties control EAC PDO formation, growth, proliferation, and activation of tumor-associated pathways that elicit stem-like properties in the cancer cells, as highlighted through in vitro and in vivo environments.
2023-10-27 | GSE240917 | GEO
Project description:Adipose stromal cells (ASCs) are the primary source of local estrogens in adipose tissue, aberrant production of which promotes estrogen receptor-positive (ER+) breast cancer. Here we show that extracellular matrix (ECM) rigidity and cell contractility are two opposing determinants for estrogen output of ASCs. Using synthetic ECMs and elastomeric micropost arrays with tunable rigidity, we find that increasing matrix compliance induces transcription of aromatase, a rate-limiting enzyme in estrogen biosynthesis. This mechanical cue is transduced sequentially by Discoidin Domain Receptor 1 (DDR1), c-Jun N-terminal kinase 1 (JNK1), and phosphorylated JunB, which binds to and activates two breast cancer-associated aromatase promoters. In contrast, elevated cell contractility due to actin stress fiber formation dampens aromatase transcription. Mechanically stimulated stromal estrogen production enhances estrogen-dependent transcription in ER+ tumor cells and promotes their growth. This novel mechanotransduction pathway underlies communications between ECM, stromal hormone output, and cancer cell growth within the same microenvironment.
2013-03-04 | GSE44811 | GEO