Convergence of YAP/TAZ, TEAD and P63 activity directs premalignant lung gene expression [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA882026 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22050634.fastq.gz | Fastqsanger.gz | |||
| SRR22050637.fastq.gz | Fastqsanger.gz | |||
| SRR22050638.fastq.gz | Fastqsanger.gz | |||
| SRR23093171.fastq.gz | Fastqsanger.gz | |||
| SRR23093172.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Convergence of YAP/TAZ, TEAD and P63 activity directs premalignant lung gene expression
| PRJNA882016 | ENA
Project description:Convergence of YAP/TAZ, TEAD and P63 activity directs premalignant lung gene expression [RNA-seq]
| PRJNA882025 | ENA
Project description:Bronchial premalignant lesions (PMLs) are composed of expanding bronchial basal cells that can progress to lung squamous cell carcinoma (LUSC) by evading immune responses. Despite ongoing efforts that have mapped gene expression and cell diversity across bronchial PML pathologies, signaling and transcriptional events driving malignancy are poorly understood. Evidence has suggested key roles for the Hippo pathway effectors YAP and TAZ and associated TEAD and TP63 transcription factor families in bronchial basal cell biology and LUSC. In this study we mapped target genes regulated by these factors by combined RNA-seq and ChIP-seq in primary human bronchial epithelial cells, revealing a converged transcriptional network that is strongly associated with bronchial PML progression. Our observations suggest that YAP/TAZ-TEAD-TP63 associate to cooperatively promote basal cell proliferation and repress signals associated with interferon responses and immune cell communication. Directly repressed targets include MHC Class II factors expressed in bronchial epithelium that correlate with adaptive immune Th1 cell activities known to contribute to the immunosuppressive microenvironment in lung cancers. Our findings provide a molecular mechanism for gene regulation in progressive PMLs that contributes to immune evasion, offering potential new avenues for lung cancer interception.
2023-05-09 | GSE213655 | GEO
Project description:Bronchial premalignant lesions (PMLs) are composed of expanding bronchial basal cells that can progress to lung squamous cell carcinoma (LUSC) by evading immune responses. Despite ongoing efforts that have mapped gene expression and cell diversity across bronchial PML pathologies, signaling and transcriptional events driving malignancy are poorly understood. Evidence has suggested key roles for the Hippo pathway effectors YAP and TAZ and associated TEAD and TP63 transcription factor families in bronchial basal cell biology and LUSC. In this study we mapped target genes regulated by these factors by combined RNA-seq and ChIP-seq in primary human bronchial epithelial cells, revealing a converged transcriptional network that is strongly associated with bronchial PML progression. Our observations suggest that YAP/TAZ-TEAD-TP63 associate to cooperatively promote basal cell proliferation and repress signals associated with interferon responses and immune cell communication. Directly repressed targets include MHC Class II factors expressed in bronchial epithelium that correlate with adaptive immune Th1 cell activities known to contribute to the immunosuppressive microenvironment in lung cancers. Our findings provide a molecular mechanism for gene regulation in progressive PMLs that contributes to immune evasion, offering potential new avenues for lung cancer interception.
2023-05-09 | GSE213654 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-05-09 | GSE213656 | GEO
Project description:BackgroundBronchial premalignant lesions (PMLs) are composed primarily of cells resembling basal epithelial cells of the airways, which through poorly understood mechanisms have the potential to progress to lung squamous cell carcinoma (LUSC). Despite ongoing efforts that have mapped gene expression and cell diversity across bronchial PML pathologies, signaling and transcriptional events driving malignancy are poorly understood. Evidence has suggested key roles for the Hippo pathway effectors YAP and TAZ and associated TEAD and TP63 transcription factor families in bronchial basal cell biology and LUSC. In this study we examine the functional association of YAP/TAZ, TEADs and TP63 in bronchial epithelial cells and PMLs.MethodsWe performed RNA-seq in primary human bronchial epithelial cells following small interfering RNA (siRNA)-mediated depletion of YAP/TAZ, TEADs or TP63, and combined these data with ChIP-seq analysis of these factors. Directly activated or repressed genes were identified and overlapping genes were profiled across gene expression data obtained from progressive or regressive human PMLs and across lung single cell RNA-seq data sets.ResultsAnalysis of genes regulated by YAP/TAZ, TEADs, and TP63 in human bronchial epithelial cells revealed a converged transcriptional network that is strongly associated with the pathological progression of bronchial PMLs. Our observations suggest that YAP/TAZ-TEAD-TP63 associate to cooperatively promote basal epithelial cell proliferation and repress signals associated with interferon responses and immune cell communication. Directly repressed targets we identified include the MHC Class II transactivator CIITA, which is repressed in progressive PMLs and associates with adaptive immune responses in the lung. Our findings provide molecular insight into the control of gene expression events driving PML progression, including those contributing to immune evasion, offering potential new avenues for lung cancer interception.ConclusionsOur study identifies important gene regulatory functions for YAP/TAZ-TEAD-TP63 in the early stages of lung cancer development, which notably includes immune-suppressive roles, and suggest that an assessment of the activity of this transcriptional complex may offer a means to identify immune evasive bronchial PMLs and serve as a potential therapeutic target.
| S-EPMC10165825 | biostudies-literature
Project description:During placentation, placental cytotrophoblast cells differentiate into syncytiotrophoblast cells and extravillous trophoblast cells. In placenta, the expression of various genes is regulated by the Hippo pathway through the transcriptional coactivator YAP/TAZ-TEAD activity. To examine the effect of YAP/TAZ and/or TEAD on trophoblast differentiation, knockdown experiments were performed. Microarray analysis were performed to identify YAP/TAZ and/or TEAD target genes in human trophoblast.
2022-07-17 | GSE182900 | GEO
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:Gene expression analysis of p63 knockdown in 2 HPV+ HNSCC cell lines using RNA-seq, Genomic profiling of p63 binding across 2 HPV+ HNSCC cell lines, Epigenomic landscape of 2 HPV+ HNSCC cell lines
2022-04-19 | GSE182133 | GEO
Project description:Dysregulation of the Hippo pathway and the consequent activation of its downstream targets, the transcriptional co-activators YAP and TAZ (YAP/TAZ), drives oncogenic transcriptional programs upon binding TEAD transcription factors in multiple human malignancies. The recent development of small molecule TEAD inhibitors (smTEADi) provides an opportunity to therapeutically target Hippo pathway dysregulation in cancer. In this regard, HPV-negative head and neck squamous cell carcinoma (HNSCC) harbor multiple genetic alterations that promote YAP/TAZ hyperactivation, raising the possibility that HNSCC cells might be dependent on YAP/TAZ-TEAD driven oncogenic transcriptional programs. To test this hypothesis, we examined the antitumor activity of the novel smTEADi, SW-682 and genetically encoded TEAD inhibitor peptide (pTEADi) in Cal33 HPV-negative HNSCC cell line-derived xenograft model. To elucidate the transcriptomic changes upon YAP/TAZ-TEAD inhibition, RNA extracted from xenograft tumors treated with SW-682 or pTEADi, as well as control, was subjected to RNA sequencing.
2024-10-01 | GSE277859 | GEO