Genome-wide analysis of gene expression in EMT cells induced by overexpression of PDGF-D compared with PC3 control cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22764 | GEO | 2010/07/07
SECONDARY ACCESSION(S): PRJNA128251
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of EMTrelated gene expression levels. The hypothesis tested in the present study was that expression of mesenchymal markers was increased and expression of epithelial markers was downregulated concomitant with increased expression of stem -like cell markers in EMT cells compared with control cells. Results demostrated that overexpression of PDGF-D induced genome-wide gene expression changes which were consistent with EMT phenotype and stem cell signatures. Total RNA isolated from stable PC3 Neo and PC3 PDGF-D cells.
2010-07-07 | E-GEOD-22764 | biostudies-arrayexpress
Project description:Epicardial cells undergo an epithelial-to-mesenchymal transtion (EMT) to generate coronary vascular smooth muscle cells (VSMC) and cardiac fibroblasts. Little is known about the mechanisms regulating EMT or the in vivo signals directing epicardial-derived cell (EPDC) fate. Here, we show that loss of PDGF signaling leads to a disruption in Sox9 expression, and when Sox9 expression was restored in mutant hearts, the EMT defect was rescued. Interestingly, mutants lacking only one of the PDGF genes exhibited a lineage specific requirement for the individual receptors. Loss of PDGFRα resulted in a deficit in cardiac fibroblast formation, while cVSMC development was unperturbed. Conversely, PDGFRβ was required for cVSMC development but not cardiac fibroblast development. Combined, our data demonstrate a novel role for PDGF receptors in epicardial EMT and EPDC development. GSM671723-GSM671724: Total RNA was isolated from E12.5 control and PDGF receptor epicardial knockout hearts using the Trizol reagent. RNA was processed as per manufacturer's instructions (Illumina Gene expression array, Illumina, inc. San Diego, CA, USA) GSM671877-GSM671882: Total RNA was isolated from E12.5 control and PDGF receptor epicardial knockout primary epicardial cultures using the Trizol reagent. RNA was processed as per manufacturer's instructions (Illumina Gene expression array, Illumina, inc. San Diego, CA, USA)
2011-02-28 | E-GEOD-27181 | biostudies-arrayexpress
Project description:Epicardial cells undergo an epithelial-to-mesenchymal transtion (EMT) to generate coronary vascular smooth muscle cells (VSMC) and cardiac fibroblasts. Little is known about the mechanisms regulating EMT or the in vivo signals directing epicardial-derived cell (EPDC) fate. Here, we show that loss of PDGF signaling leads to a disruption in Sox9 expression, and when Sox9 expression was restored in mutant hearts, the EMT defect was rescued. Interestingly, mutants lacking only one of the PDGF genes exhibited a lineage specific requirement for the individual receptors. Loss of PDGFRα resulted in a deficit in cardiac fibroblast formation, while cVSMC development was unperturbed. Conversely, PDGFRβ was required for cVSMC development but not cardiac fibroblast development. Combined, our data demonstrate a novel role for PDGF receptors in epicardial EMT and EPDC development.
2011-02-28 | GSE27181 | GEO
Project description:Understanding and controlling stem cell differentiation in vitro is critical for the development of stem cell-based therapies. We have previously shown that platelet-derived growth factor AA (PDGF-AA) stimulates the expansion of neuronal progenitors from neural stem cells, but is unable to replace fibroblast-growth factor 2 (FGF-2) as a stem cell mitogen. In the present study, we compared gene expression in neural stem cells that were grown in the presence of FGF-2 to that of cells cultured with PDGF-AA or in the absence of growth factor, which induces differentiation. Most of the transcripts enriched in FGF-2-treated cells were connected to cell division (70%) and showed limited overlap with previously described stem cell transcriptional signatures. PDGF-AA significantly regulated 156 genes, 146 of which were also modified by differentiation in the absence of growth factor. The latter condition affected the expression of 153 additional genes which were regulated less than two fold by PDGF-AA. Among the genes induced by differentiation was the PDGF-A gene itself, suggesting that in the absence of exogenously added growth factors, cells make their own PDGF-AA in an autocrine manner. In addition, we identified several poorly characterized transcripts that were highly regulated and may play a role in stem cell differentiation. Our results suggest that the genetic program elicited by PDGF-AA is not unique, but an intermediate between the ones of FGF-2-cultured stem cells and differentiated cells. These observations are compatible with the hypothesis that PDGF-AA induces a partial differentiation of neural stem cells, which retain the ability to proliferate. Keywords: treatment comparison
2006-03-12 | GSE3251 | GEO
Project description:Cyclin D1 is a well characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in ‘inhibitor of differentiation 1’ (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1 independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 and ID1 gene expression were associated with mesenchymal-markers including SNAI1, SNAI2 and TWIST1, and with clinicopathological parameters. Finally, a greater percentage of CCND1low/ID1high tumours were found in the EMT-like ‘claudin-low’ subtype of breast cancer than in other subtypes. Together, these results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id1 and is linked to an increase in EMT markers. Moreover, we have confirmed a relationship between cyclin D1, Id1 and EMT in primary breast cancer, supporting our in vitro findings that low cyclin D1 expression can be linked to aggressive features in subgroups of breast cancer. MDA-MB-231 cells were transfected with cyclin D1, CDK4/6 or control siRNA.
2011-10-12 | E-GEOD-27260 | biostudies-arrayexpress
Project description:Numerous cytokines have been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal interaction. Growing evidence suggests that platelet-derived growth factor (PDGF) signaling is an important mediator of these interactions. The purpose of this study was to evaluate the effect of PDGF-α on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats underwent bowel transection, Sham-PDGF-α rats underwent bowel transection and were treated with PDGF-α, SBS rats underwent a 75% bowel resection, and SBS-PDGF-α rats underwent bowel resection and were treated with PDGF-α. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. Illumina's Digital Gene Expression (DGE) analysis was used to determine PDGF-related gene expression profiling. PDGF-α and PDGF-α receptor (PDGFR-α) expression was determined using Real Time PCR. Western blotting was used to determine p-ERK, Akt1/2/3, bax and bcl-2 protein levels. SBS rats demonstrated a significant increase in PDGF-α and PDGFR-α expression in jejunum and ileum compared to sham animals. SBS-PDGF-α rats demonstrated a significant increase in bowel and mucosal weight, villus height and crypt depth in jejunum and ileum compared to SBS animals. PDGF-α expression in crypts increased in SBS rats (vs sham) and was accompanied by increased cell proliferation following PDGF-α administration. A significant decrease in cell apoptosis in this group was correlated with lower bax protein levels. In conclusion, in a rat model of SBS, PDGF-α stimulates enterocyte turnover, which is correlated with up-regulated PDGF-α receptor expression in the remaining small intestine.
2012-02-29 | GSE36122 | GEO
Project description:The conversion of an epithelial cell to a mesenchymal cell is critical to vertebrate embryogenesis and a defining structural feature of organ development, such as forming fibroblasts in injured tissues, or in initiating metastases in epithelial cancer. From a general perspective, EMT is about disaggregating epithelial units and reshaping epithelia for movement. This phenotypic conversion requires the molecular reprogramming of epithelia with new biochemical instructions. It is known that commonly used molecular markers for EMT include increased expression of N-cadherin and vimentin, nuclear localization of beta-catenin, and increased production of the transcription factors such as Snail, Twist, and SIP1/ZEB2. Much of this conversion, however, has been studied during experiments that expose new transduction and signaling pathways in epithelia, and more recently in fibrogenic tissues. It is not yet clear whether the fibroblast transition of EMT is an expected middle phase of transdifferentiating epithelia, or whether EMT producing fibroblasts is an arrested form of transdifferentiation. EMT is easily engaged by a combination of cytokines associated with proteolytic digestion of basement membranes upon which epithelia reside. We analyzed PCA and hierarchical clustering method of the gene expression pattern of the renal tubular cells and mammary gland cells. We then identified the genes which discriminate between the renal tubular and the mammary gland epithelial cells (PC1), or EMT-induced and non-induced cells (PC3). Undergoing EMT identifies the genes that discriminate between the renal tubular and the mammary gland epithelial cells(PC1), or EMT-induced and non-induced cells (PC3). Affymetrix GeneChip Mouse Genome 430 2.0 Array was used to transcriptionally profile to compare mouse EMT-induced cells and non-induced cells.
2011-08-12 | E-GEOD-31359 | biostudies-arrayexpress
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. Comparison of S17 stromal cells treated with PDGF-BB for 72h to control
2011-12-04 | E-GEOD-33717 | biostudies-arrayexpress
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis.
2011-12-04 | GSE33717 | GEO
Project description:SILAC analysis of human primary bladder smooth muscle cells treated with platelet-derived growth factor for 0, 4, and 24 h. Platelet-derived growth factor-BB (PDGF-BB) is a mitogen and motogen that has been implicated in the proliferation, migration and synthetic activities of smooth muscle cells (SMC) that characterize pathologic tissue remodeling in hollow organs. To explore the signals induced by PDGF on a global scale, we performed expression profiling and quantitative proteomics analysis of PDGF-treated human visceral SMC. 1695 genes and 241 proteins were identified as differentially expressed in PDGF-treated primary bladder SMC versus non-treated cells. Analysis of gene expression data revealed MYC, JUN, EGR1, MYB and RUNX1 as the transcription factors most significantly networked with upregulated genes; DDIT3, NFAT5, and SOX5 were most networked with downregulated genes. For protein identification and quantification, raw mass spectrometric data were analyzed with MaxQuant software (version 1.0.13.13). The parameters were set as follows. In the Quant module, SILAC triplets was selected; oxidation (M) and acetyl (Protein N-term) were set as variable modification; carbamidomethyl (C) was set as fixed modification; concatenated IPI human database (version 3.52) (74,190 forward sequences and 74,190 reverse sequences) was used for database searching; all other parameters were default. Tandem mass spectra were searched by Mascot (version 2.2.0.4) (Matrix Science, Boston, MA). In the Identify module, all parameters were default, except that maximal peptide posterior error probability was set as 0.05. False discovery rates for protein and peptide identifications were both set at 0.01.
2014-08-04 | PXD000624 | Pride