Whole lungs: TAZ-deficient mice and their littermates
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE10805 | GEO | 2009/08/01
SECONDARY ACCESSION(S): PRJNA107391
REPOSITORIES: GEO
Similar Datasets
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
Project description:Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are dictated by YAP/TAZ-TEAD – a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2, and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fueling nutrient mTORC1 signaling. By orchestrating the transcription of a repertoire of cell-surface transporters, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 pathway activation. Dissociating mTORC1 from these nutrient inputs – elicited by the loss of Rag GTPases – inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. These findings define a pivotal role for YAP/TAZ-TEAD in steering endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
2022-05-08 | PXD026872 | Pride
Project description:Transcriptome profiling of human umbilical vein endothelial cells (HUVECs) overexpressing constitutively nuclear YAP (YAP S127A), TAZ (TAZ S89A) or TEAD-binding deficient YAP (YAP S94A/S127A) or TAZ (TAZ S51A/S89A) to identify YAP and TAZ target genes.
2022-05-02 | GSE163456 | GEO
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
Project description:The NF2 gene, which encodes the Merlin protein, is a bona fide tumor suppressor whose mutations underlie inherited tumor syndrome Neurofibromatosis Type 2 (NF2). Recent large-scale genome sequencing studies have also identified NF2 as one of the most frequently mutated genes in VHL-wild-type kidney cancers. Even though a wide array of downstream signaling pathways has been described for Merlin/NF2, the molecular mechanisms underpinning the growth and survival of NF2 mutant tumors remain poorly understood. Using an inducible orthotopic kidney tumor model, we demonstrate for the first time that silencing of YAP/TAZ is sufficient to induce regression of pre-established NF2 deficient kidney tumors. Mechanistically, we show that YAP/TAZ ablation severely diminishes glycolysis by downregulating the transcription of several glycolytic enzymes and growth factors and RTK-PI3K-AKT signaling, resulting in growth arrest. On the other hand, YAP/TAZ depletion significantly increases mitochondrial respiration and overproduction of mitochondrial ROS, resulting in redox imbalance and oxidative stress cell death when challenged by nutrient stress. Furthermore, we identify lysosome-mediated cAMP-PKA/EPACdependent activation of the RAF-MEK-ERK pathway to be a novel resistance mechanism that allows NF2 deficient tumor cells to survive YAP/TAZ inhibition in vitro and in vivo. Finally, unbiased analysis of TCGA primary kidney tumor transcriptomes confirms strong correlations of a YAP/TAZ signature with the expression of glycolysis, oxidative phosphorylation and lysosomal genes, validating the clinical relevance of our findings.
2019-05-04 | GSE125408 | GEO
Project description:whole lungs: TAZ-deficient mice and their littermates
| PRJNA107391 | ENA
Project description:Phosphodiesterase type 5 inhibitors (PDE5is) are the primary therapeutic option for erectile dysfunction. However, 30% of patients do not respond to PDE5is treatment, making the quest for a new treatment modality a central endeavor. Here, we found a new pathway in erectile function control, mechano-regulated YAP/TAZ activate Adrenomedullin transcription, which sustains smooth muscle cells (SMCs) relaxation to maintain the erection. We first found that penile erection stretches the SMCs, dominating YAP/TAZ activity. Subsequently, we showed that YAP/TAZ plays a vital role in erectile function and penile rehabilitation using genetic lesions and several animal models. The mechanism relies on the regulation of Adrenomedullin on penile SMCs contraction, which we identify here as a direct YAP/TAZ transcript. Notably, conventional PDE5is targeting NO-cGMP signaling do not cure YAP/TAZ deficient ED. In contrast, by activating YAP/TAZ-Adrenomedullin cascade, mechano-stimulation improved erectile function, including PDE5is non-responders in both experimental models and clinical trials. Our studies lay the groundwork for exploring mechano-YAP/TAZ-Adrenomedullin as prospective targets in the treatment of ED
2023-03-31 | GSE208293 | GEO
Project description:Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells to lose cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lungs. Significantly, this cell fate conversion is mediated via distinctive transitional cell states of Damage-Associated Transient Progenitors (DATPs), recently known to emerge during injury repair, in mouse and human lungs. Further, YAP/TAZ signaling is identified to realign the amino acid metabolism by modulating mTORC1-ATF4 activity, which is integral to fate conversion of secretory cells into AT1 fate. We observed aberrant activation of the YAP/TAZ-mTORC1-ATF4 axis in the altered airway epithelium of human pulmonary fibrosis where the emergence of DATPs and A1 cells is prominent. Finally, genetic and pharmacologic inhibition of mTORC1 activity restores lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases.
2021-06-25 | GSE178829 | GEO
Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage derived sarcomas with poor prognosis. The molecular events underlying SC lineage cells-to-MPNST transformation remain elusive. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyper-proliferation. Conversely, disruption of TAZ/YAP activity alleviates tumor burden in Lats1/2-deficient mice and inhibits human MPNST cell proliferation. Moreover, genome-wide target profiling reveals that TAZ/YAP-TEAD1 directly activates a set of oncogenic programs in SCs including PDGFR/RAF signaling. Co-targeting TAZ/YAP and PDGFR/RAF signaling efficaciously reduces tumorigenicity in Lats1/2-deficient tumors. Thus, our findings establish a previously unrecognized convergence between LATS1/2-TAZ/YAP pathway and MPNST pathogenesis, suggesting that combined inhibition of TAZ/YAP-PDGFR/RAF signaling may be beneficial in MPNSTs.
2018-02-13 | GSE99040 | GEO
Project description:To identify cellular and genetic abnormalities involved in interstrand cross link repair-deficient bone marrow failure and its transformation to leukemia, we used an Ercc1 hypomorphic mouse model (Ercc1 -/d). Gene expression profiling was done to determine which genes are differentially expressed
2015-03-24 | GSE47700 | GEO