Gene expression signatures for mSCLC cell lines derived from Rb/P53 mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE76813 | GEO | 2019/01/13
REPOSITORIES: GEO
Similar Datasets
Project description:Tissue Factor Pathway Inhibitor-2 is Induced by Fluid Shear Stress in Vascular Smooth Muscle Cells and Affects Cell Proliferation and Survival Introduction: Vascular smooth muscle cells (SMCs) are exposed to fluid shear stress (FSS) after interventional procedures such as balloon-angioplasty. Whereas the effects of hemodynamic forces on endothelial cells are explored in detail, the influence of FSS on smooth muscle cell function is poorly characterized. Here, we investigated the effect of FSS on SMC gene expression and function. Methods: Laminar FSS of arterial level (14 dynes/cm2) was applied to SMC cultures for 24 h in a parallel-plate flow chamber. The effect of FSS on gene expression was first screened with microarray technology and the results further verified by real time (RT) PCR and immunoblotting. Protein expression was also studied in the rat carotid artery after balloon-injury and DNA synthesis and apoptosis was examined in SMCs in vitro. Results: Microarrays identified tissue-pathway inhibitor-2 (TFPI-2) as the most differentially expressed gene by FSS in cultured SMCs. The regulatory effect of FSS on the expression of TFPI-2 was confirmed by RT-PCR and immunobloting demonstrating a more than 400-fold increase in TFPI-2 expression in SMCs exposed to FSS compared to static controls and a consistent upregulation at the protein level. Functionally, SMC proliferation was decreased by FSS and recombinant TFPI-2 was found to inhibit SMC proliferation and induce SMC apoptosis as indicated by activation of caspase-3. In vivo, TFPI-2 expression was found to be up-regulated 5, 10 and 20 h after rat carotid balloon-injury and immunohistochemistry demonstrated TFPI-2 protein in luminal SMCs exposed to FSS in rat carotid intimal hyperplasia 10 days after balloon-injury. Conclusion: FSS strongly influence gene expression in cultured SMCs and induce TFPI-2 expression, which is also expressed after rat carotid balloon injury in luminal SMCs exposed to FSS. Functionally, TFPI-2 may play an important role in vessel wall repair by regulating SMC proliferation and survival. Further studies are needed to elucidate the mechanisms by which TFPI-2 control SMC function. 3 x 2 samples from a paired fluid shear stress experiment on smooth muscle cells.
2010-04-12 | E-GEOD-19909 | biostudies-arrayexpress
Project description:ATAC-seq in paired SMC vs. Non-SMC
| PRJNA664053 | ENA
Project description:Poor prognosis of small cell lung cancer (SCLC) is mainly attributed to its highly metastatic capability. Here we identify the SMC and Non-SMC from Rb1L/L/Trp53 L/L mouse model through FACS with NE and mensenchymal markers. In order to identify functions of these two subpopulations during SCLC malignant progression, we compared their metastatic capability by allograft experiment. In addition, we find that the SMC is progressively transited from the Non-SCLC during mouse SCLC malignant progression. Further investigation reveals that genetic disruption of the SWI/SNF chromatin-remodeling complex, in RP model abrogates SMC phenotype maintenance and SCLC metastasis. In search of important downstream regulators, we find that TAZ, the core transcription cofactor of the Hippo pathway, is epigenetically silenced by SWI/SNF complex during this process. Collectively, our data link phenotypic transition to cancer metastasis and identify TAZ as a critical molecular switch that controls SCLC plasticity.
2022-08-24 | GSE158293 | GEO
Project description:Poor prognosis of small cell lung cancer (SCLC) is mainly attributed to its highly metastatic capability. Here we identify the SMC and Non-SMC from Rb1L/L/Trp53 L/L mouse model through FACS with NE and mensenchymal markers. In order to identify functions of these two subpopulations during SCLC malignant progression, we compared their metastatic capability by allograft experiment. In addition, we find that the SMC is progressively transited from the Non-SCLC during mouse SCLC malignant progression. Further investigation reveals that genetic disruption of the SWI/SNF chromatin-remodeling complex, in RP model abrogates SMC phenotype maintenance and SCLC metastasis. In search of important downstream regulators, we find that TAZ, the core transcription cofactor of the Hippo pathway, is epigenetically silenced by SWI/SNF complex during this process. Collectively, our data link phenotypic transition to cancer metastasis and identify TAZ as a critical molecular switch that controls SCLC plasticity.
2022-08-24 | GSE158290 | GEO
Project description:Poor prognosis of small cell lung cancer (SCLC) is mainly attributed to its highly metastatic capability. Here we identify the SMC and Non-SMC from Rb1L/L/Trp53 L/L mouse model through FACS with NE and mensenchymal markers. In order to identify functions of these two subpopulations during SCLC malignant progression, we compared their metastatic capability by allograft experiment. In addition, we find that the SMC is progressively transited from the Non-SCLC during mouse SCLC malignant progression. Further investigation reveals that genetic disruption of the SWI/SNF chromatin-remodeling complex, in RP model abrogates SMC phenotype maintenance and SCLC metastasis. In search of important downstream regulators, we find that TAZ, the core transcription cofactor of the Hippo pathway, is epigenetically silenced by SWI/SNF complex during this process. Collectively, our data link phenotypic transition to cancer metastasis and identify TAZ as a critical molecular switch that controls SCLC plasticity.
2022-08-24 | GSE158091 | GEO
Project description:Differential gene expression in paired SMC vs. Non-SMC
| PRJNA664763 | ENA
Project description:Unlike other terminally differentiated cell types, vascular SMCs display remarkable phenotypic plasticity. The adult, differentiated state is traditionally defined by expression of well-characterized SMC contractile genes. Extracellular cues, however, can induce contractile SMCs to remodel toward a synthetic state characterized by a spectrum of proliferative, migratory, and inflammatory phenotypes. We used whole-genome expression arrays to to identify genes associated with SMC phenotypic modulation. Experiment Overall Design: Rat aortic SMCs were serum-starved for 72 hours and subsequently treated with either PDGF-BB or its respective vehicle (n=2). RNA samples were hybridzed to Affymetrix arrays with the intent to identify early genes associated with SMC phenotypic modulation.
2009-12-02 | E-GEOD-19106 | biostudies-arrayexpress
Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC transdifferentiation into macrophage-like SMCs. Furthermore, during transdifferentiation, the SMCs' expression of PADI4 upregulating and SMC generated extracellular trap, a web-like structure, which plays key role in the development of atherosclerosis plaque. To reveal the potential mechanism of the SMC derived macrophages generated ETs surducing surrounding SMCs within the media of artery during the process of atherosclerosis plaque development, we utilized the dsDNA and H3CIT protein to stimuli the SMCs, the SMC stimulated with 0.2%BSA as coontrol group, we collect the cells and did RNA-sequencing between two groups to find the potential signaling pathway participating in the process
2022-11-04 | GSE197074 | GEO
Project description:Smooth muscle cells (SMCs) display dynamic plasticity by changing phenotype under various pathophysiological conditions. Uncovering how SMCs regulate their phenotype is a key to understanding the molecular mechanisms of a number of gastrointestinal diseases. MicroRNAs (miRNAs), generated in cells by Dicer, have been identified as regulators of the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal SMCs in a transgenic animal model. We generated SMC-specific Dicer (smDicer) null animals that express the reporter, green fluorescence protein (eGFP), in a SMC-specific manner. eGFP labeled SMCs were used for morphological, cytometric and genetic studies of smDicer null mutant and wild type control mice. The structure of the bowel wall was examined by confocal microscopy, and function was evaluated by recording spontaneous and evoked contractions. SMCs were purified with fluorescence-activated cell sorting and SM specific gene expression studies were performed with genechip arrays, PCR and quantitative PCR. Bioinformatic analyses were used to characterize the interaction between miRNAs and target genes. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs. Profiling and bioinformatic analyses showed SMC phenotype is regulated by a complex network of positive and negative feedback by SM miRNAs, serum response factor (SRF), and other transcriptional factors. SM miRNAs play an important role in growth, development and survival of SMCs. Phenotypic changes of SMCs may be regulated through multiple pathways in an interaction network of SM miRNAs, SRF, and additional transcriptional factors. We used microarrays to identify genetic changes during the development of gastric smooth muscle cells in the smDicer null mice. Mouse mRNA microarrays were performed on GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix). Total RNAs isolated from the jejunal muscularis of the smDicer knockout (KO) and the wild type (WT) control mice at the ages of ~3 weeks were used for the arrays. The cDNA synthesis, hybridization, cDNA labeling, and scanning were performed. Gene expression between the smDicer KO and the WT controls were compared.
2010-06-08 | E-GEOD-21738 | biostudies-arrayexpress
Project description:Smooth muscle cells (SMCs) and endothelial cells (ECs) constitute vasculature media and endothelium, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but also damage the protective endothelial lining, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMCs versus ECs) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFα or IL-1β, both established inducers of SMC hyperplasia and EC dysfunction. To analyze combined SMC/EC transcriptomes we developed customized algorithms. Induced by TNFα or IL-1β, 212 and 263 genes respectively showed greater up-regulation in SMCs than in ECs (SMC-enriched), while 140 and 204 genes showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene interaction networks identified 5 common hubs and 4 common bottlenecks in the two SMC-enriched gene sets, and 8 hubs and 3 bottlenecks shared in the EC-enriched gene sets. Significantly, four gene modules were formed with these hubs and bottlenecks. While the JUN module (including JUN, KLF5, HIF1A, CXCL8, FOSL1) and FYN module (FYN, JAK2, MAP2, PIK3R3, DAB2, ASAP2) were SMC-enriched, the SMAD3 (SMAD3, CDKN1A, TRAF1, BCL6, CEBPD, TRIB3, ANK3) and XPO1 (XPO1, ETS2, SSH2, NDRG1, GFPT2?) modules were EC-enriched. As these core subnetworks respond to pathogenic stimulation in a SMC-versus-EC differential manner, they may inform potential intervention targets for selective mitigation of SMC hyperplasia without endothelial damage.
2018-02-14 | GSE96962 | GEO