Similar Datasets
Project description:Here, we report that YAP-overexpression inhibits the establishment of the pluripotency network.
2019-05-16 | GSE131232 | GEO
Project description:RNA-seq analysis of YAP-overexpressing mouse embryonic fibroblasts
| PRJNA543022 | ENA
Project description:The transcriptional coactivator YAP is the key downstream effector of the Hippo pathway. YAP overexpression in the developing mouse brain results in excessive expansion of the neural progenitor pool and severe perturbation of brain development. Nf2/Merlin is a tumor suppressor whose mutations are found in many human cancers. Loss of Merlin during brain development causes overexpansion of the neural progenitor pool. We used microarrays to identify the gene expression changes caused by YAP overexpression and Nf2 deletion. We used a double-transgenic system to overexpress YAP in the developing mouse brain by crossing mice carrying a doxycycline-dependent allele of YAP1-S127A (TetO-YAP1) with those expressing the reverse tetracycline-dependent transactivator rtTA under the control of the neural progenitor-specific Nestin promoter (Nes-rtTA) and feeding the dam with doxycycline-containing food (200 mg/kg) from E7.5. We conditionally deleted Nf2 using the telencephalon-specific Emx1-Cre.
2013-06-19 | E-GEOD-48078 | biostudies-arrayexpress
Project description:Recent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
2008-06-12 | E-GEOD-2684 | biostudies-arrayexpress
Project description:This study compares gene expression change upon expression of Yes-associated protein (YAP) wild-type or mutants in order to establish the importance of TEAD binding and WW domains in the gene-induction function of YAP. The results indicate that gene-induction is seriously comprised in YAP-S94A (TEAD binding domain mutant) expressing cells. And mutantion of WW domains (YAP-W1W2) also affect a fraction of YAP induced genes. Therefore both TEAD binding domain and WW domains are required for the full function of YAP in gene-induction. Experiment Overall Design: Four samples are included: 1. pQCXIH vector control; 2 YAP-WT expression; 3. YAP-S94A expression; 4. YAP-W1W2 expression. Gene expression profiles of YAP wild-type or mutants expressing cells were compared to that of vector control. Experiments were done in MCF10A mammary epithelial cells.
2010-01-19 | E-GEOD-13218 | biostudies-arrayexpress
Project description:The transcriptional coactivator YAP is the key downstream effector of the Hippo pathway. YAP overexpression in the developing mouse brain results in excessive expansion of the neural progenitor pool and severe perturbation of brain development. Nf2/Merlin is a tumor suppressor whose mutations are found in many human cancers. Loss of Merlin during brain development causes overexpansion of the neural progenitor pool. We used microarrays to identify the gene expression changes caused by YAP overexpression and Nf2 deletion.
2013-06-19 | GSE48078 | GEO
Project description:The transcriptional coactivator Yap promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. Here we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal expansion, as proliferation is counterbalanced by increased apoptosis. To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required. In response to liver injury, Yap drives clonal expansion, suppresses hepatocyte differentiation and promotes a progenitor phenotype. These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair. Totally sixteen samples
2015-02-07 | E-GEOD-65207 | biostudies-arrayexpress
Project description:YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes. PUBLICATION ABSTRACT:; The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Experiment Overall Design: MCF10A cells were infected with retrovirus constructs (vector or YAP) and puromycin was used to select for transduced cells. Cells were split and grown to ~60-75%% confluency at which point they were harvested for RNA. Vector vs. YAP comparison was done in duplicate.
2008-06-11 | E-GEOD-10196 | biostudies-arrayexpress
Project description:siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA. Loss of contact inhibition and anchorage-independent growth are hallmarks of cancer cells. In this context, frequent inactivation of the Hippo pathway and subsequent nuclear enrichment of the transcriptional coactivator yes-associated protein (YAP) uncouple cell proliferation and anti-apoptosis from contact inhibition, associated with uncontrolled tumor growth and tumor cell dissemination. However, general molecular mechanisms of tumor-supporting YAP activity remain unclear. In this study, we show that overexpression and nuclear accumulation of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells leads to an induction of the Notch pathways through transcriptional activation of the Notch ligand jagged-1 (Jag-1). This induction of Jag-1 strictly depends on binding of YAP to TEAD4 and does not rely on WNT/β-catenin pathway activity. Co-activation of YAP, TEAD4, Jag-1, and the Notch target gene Hes-1 was significantly higher in HCC from patients with poor prognosis. High-level expression and nuclear accumulation of YAP correlates with Jag-1/Notch activation not only in human HCC tissues, but also in colon and pancreatic cancer tissues. Thus, our data demonstrate that YAP-driven co-activation of the Jag-1/Notch pathway in part facilitates oncogenic properties of the oncogene YAP not only in HCC but also in different gastrointestinal malignancies. Expression profiling of untreated HCC cell lines (control 1), cells transfected with scrambled/nonsense siRNA (control 2), and after siRNA-mediated YAP inhibition.
2012-11-01 | E-GEOD-35004 | biostudies-arrayexpress
Project description:We aimed to identify microRNAs that are regulated by YAP in human mammary epithelial cells. We utilized deep sequencing technology to identify microRNAs that are induced by YAP overexpression and repressed by YAP knockdown.
2012-10-01 | E-GEOD-41124 | biostudies-arrayexpress