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Next Generation Sequencing identifies TAZ transcriptional targets in tumor derived isogenic cells

ABSTRACT: To gain a broader perspective of the underlying biological processes used by TAZ-dependent (TAZDEP) and TAZ-independent (TAZIND) cells for the maintenance of their BCSC phenotypes, we performed an RNA-seq analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168672 | GEO | 2021/06/11

REPOSITORIES: GEO

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Next Generation Sequencing identifies TAZ transcriptional targets in tumor derived isogenic cells

Project description:Next Generation Sequencing identifies TAZ transcriptional targets in tumor derived isogenic cells

| PRJNA713361 | ENA

Next generation RNA-sequencing of YAP and TAZ knockdowns in mel537 melanoma cells

Project description:The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) data sets between siScrambled negative control groups and YAP, TAZ, or YAP/TAZ knockdown groups

2020-09-30 | GSE146918 | GEO

Next-Generation Sequencing Identifies Potential Actionable Targets in Paediatric Sarcomas.

Project description:Background: Bone and soft-tissue sarcomas represent 13% of all paediatric malignancies. International contributions to introduce next-generation sequencing (NGS) approaches into clinical application are currently developing. We present the results from the Precision Medicine program for children with sarcomas at a reference centre. Results: Samples of 70 paediatric sarcomas were processed for histopathological analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) with a consensus gene panel. Pathogenic alterations were reported and, if existing, targeted recommendations were translated to the clinic. Seventy paediatric patients with sarcomas from 10 centres were studied. Median age was 11.5 years (range 1-18). Twenty-two (31%) had at least one pathogenic alteration by NGS. Thirty pathogenic mutations in 18 different genes were detected amongst the 22 patients. The most frequent alterations were found in TP53, followed by FGFR4 and CTNNB1. Combining all biological studies, 18 actionable variants were detected and six patients received targeted treatment observing a disease control rate of 78%. Extrapolating the results to the whole cohort, 23% of the patients would obtain clinical benefit from this approach. Conclusions: Paediatric sarcomas have a different genomic landscape when compared to adult cohorts. Incorporating NGS targets into paediatric sarcomas' therapy is feasible and allows personalized treatments with clinical benefit in the relapse setting.

| S-EPMC8067272 | biostudies-literature

Next-generation mRNA sequencing of MKL-1 Merkel cell carcinoma cells expressing wild-type or mutant YAP or TAZ

Project description:The overarching goal of this study was to characterize TEAD-dependent transcriptional effects of YAP and TAZ in Merkel cell carcinoma cells. To that end, transcriptional profiling was performed on MKL-1 cells induced to express GFP, wild-type YAP or TAZ, or YAP S94A or TAZ F52A for 3 days.

2023-01-29 | GSE189054 | GEO

Characterization of the interactomes of YAP and TAZ in podocytes identifies a relation between YAP and TAZ and proteins of the nuclear shuttling machinery

Project description:The two effector proteins of the Hippo signaling pathway, YAP and TAZ, play a pivotal role in the cellular homeostasis of podocytes and in the pathogenesis of focal segmental glomerulosclerosis (FSGS). We aim to unravel the unique and redundant functions of YAP and TAZ in the podocyte by identifying podocyte-specific interactors. We generated stable heat sensitive mouse podocytes (hsMPs) carrying a single copy integration of a transgenic construct expressing a flagged version of mouse Yap (3XFLAG.YAP), Taz (3XFLAG.TAZ) or Ruby (3XFLAG.RUBY) in the Rosa26 locus. To explore the interactome of YAP and TAZ in podocytes we immunoprecipitated the tagged proteins and characterized the co-immunoprecipitated protein complexes by mass spectrometry. Within the interactome analyses of the hsMPs, we identified shared and non-shared interacting proteins between YAP and TAZ. Among these identified proteins many well established interactors of YAP and TAZ were included, like proteins of the Tead family, different angiomotins or large tumor suppressor kinase 1 (Lats1). Strikingly, among the shared proteins were numerous proteins of the nuclear shuttling machinery, like importins (Ipo), exportins (Xpo), transportins (Tnpo) and nucleoporins (Nup) that form the nuclear pore complex (NPC), such as NUP107, NUP133, NUP205 and XPO5.

2024-01-26 | PXD040448 | Pride

ChIP-seq for TAZ (WWTR1) binding region in C2C12 myoblasts

Project description:We demonstrated that TAZ positively regulates Irs1 gene transcription in muscle. Therefore we designed ChIP-seq experiment to reveal detailed mechanism of regulation. To capture TAZ in chromatin preparation, we made Flag-tagged TAZ expressing and control vector transduced C2C12 cells by retroviral infection. We used FLAG-conjugated beads to capture TAZ-chromatin complexes and ChIP-seq was perforemd. Among many TAZ binding sites, we focused Irs1 regulatory region because our primary purpose was to identify TAZ binding site for the regulation of Irs1 transcription.

2018-12-13 | E-MTAB-6764 | biostudies-arrayexpress

Yap and Taz regulate retinal pigment epithelial cell fate

Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.

2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress

The effect of YAP/TAZ knockdown on the intestinal epithelium

Project description:The Hippo pathway plays a crucial in organ size control during development and tissue homeostasis in adult life. To examine a role for Hippo signaling in the intestinal epithelium, we analyzed gene expression patterns in the mouse intestinal epithelilum transfected with siRNAs or expression plasmids for shRNAs targeting the Hippo pathway effectors, YAP and TAZ. We performed two independent series of experiments (siGFP (n=3) vs siYAP/siTAZ (n=3), and shLacZ (n=1) vs shYAP/shTAZ (n=1)). Control siRNA (siGFP), YAP/TAZ siRNAs, or expression plasmids for control shRNA (shLacZ) or YAP/TAZ shRNAs were introduced into the mouse intestinal epithelium by the newly-developed in vivo transfection method. Four days after transfection, intestinal epithelial cells were isolated from the tissues and total RNA was extracted.

2014-07-18 | E-GEOD-45155 | biostudies-arrayexpress

Transcription profiling of mouse whole lung from TAZ-deficient mice and their littermates

Project description:TAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms. Experiment Overall Design: Four total RNA samples from E15.5 lungs were mixed for each group.

2009-08-08 | E-GEOD-10805 | biostudies-arrayexpress

Regulation of gene expression by the Hippo effectors, Taz and Yap, in muscle stem cells

Project description:The Hippo pathway downstream effectors, Yap and Taz, play key roles in cell proliferation and tissue growth, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed gene expression changes driven by Taz and compared these to Yap mediated changes to the transcriptome by measurement of gene expression on Affymetrix microarrays. To interrogate overlapping and unique transcriptional changes driven by these Hippo effectors, satellite cell-derived myoblasts were transduced with constitutively active TAZ S89A or YAP S127A retrovirus for 24h or 48h, with empty retrovirus as control. Triplicate microarray analyses of empty vector controls, hYAP1 S127A and TAZ S89A transgenic primary myoblasts were conducted.

2017-06-20 | E-MTAB-5395 | biostudies-arrayexpress

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