Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA371811 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To investigate the role of Hippo-YAP signaling in angiogenesis, we performed RNA-sequencing by using brain ECs isolated from mice with EC-specific deletion of indicated components of Hippo pathway.
2017-08-22 | GSE94673 | GEO
Project description:To investigate the role of Hippo-YAP signaling in angiogenesis, we performed RNA-sequencing by using lung ECs isolated from mice with EC-specific deletion of indicated components of Hippo pathway.
2017-08-22 | GSE94685 | 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:RNA-sequencing of lung ECs isolated at P5 from mice with EC-specific deletion of LATS1/2 and LATS1/2;YAP/TAZ
| PRJNA371812 | ENA
Project description:Endothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood-brain barrier (BBB) disruption. ECs comprising the BBB are known to have a higher mitochondrial volume compared with peripheral ECs. In previous study, we reported Tek-CRIF1-knockout (KO) mice, with EC-specific deletion of the mitochondrial OxPhos-related gene, Crif1, also known as Gadd45gip1 (encoding GADD45G-interacting protein 1), display profound BBB defects accompanied by reduced expression of junctional proteins in ECs. To identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from Tek-CRIF1 mice. This transcriptome analyses of the Tek-CRIF1-KO mouse revealed significant changes in some signaling, a pathway intimately involved in BBB maintenance.
2022-08-31 | GSE207106 | GEO
Project description:Proper lung function relies on precisely balanced numbers of specialized epithelial cell types that work together and are maintained in homeostasis. In this study we have described essential roles for the transcriptional regulators YAP and TAZ, which are key effectors of Hippo pathway signaling, in maintaining lung epithelial homeostasis. Phenotypes associated with Yap/Taz deletion include alveolar defects and a striking development of goblet cell metaplasia throughout the airways. Lineage specific deletion of Yap and Taz in Scgb1a1+ cells leads to increased Mucin production within the knockout cells in vivo. In order better characterize the in vivo transcriptional changes associated with Yap/Taz knockout in these cells, we have isolated Scgb1a1 lineage traced cells from control and yap/taz cNull mice and performed bulk RNA sequencing.
2021-08-09 | GSE171712 | GEO
Project description:<p>The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer. </p>
2020-06-29 | MTBLS1764 | MetaboLights
Project description:Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.
2017-06-13 | PXD005751 | Pride
Project description:Background & Aims The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are promising targets for cancer therapy. However, it is not understood if inhibition of one factor is compensated by the activation of the other and if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver-resident cells. Methods Mice with hepatocyte (HC)-/biliary epithelial cell (BEC)-specific deletions of YAP and/or TAZ were generated (YAPKO, TAZKO and double knock-out (DKO)). Liver tissues were investigated by histology, immunohistochemistry, and single cell RNA-sequencing (scRNA-seq). Serum samples were analyzed using a cytokine array. Results Liver tissues from YAPKO and DKO mice were characterized by the loss of BECs, liver fibrosis, and necrosis. This phenotype was weakened in DKO tissues compared to specimen from YAPKO animals. YAP expression was induced in different non-parenchymal cells (NPCs) after YAP-depletion in HCs and BECs. Activation of YAP in Kupffer cells (KCs) and endothelial cells (ECs) in subclusters with specific molecular features was independent of cholestasis. Pro-inflammatory chemokines and cytokines such as interleukin-1 (IL1) and intercellular adhesion molecule-1 (ICAM1) were detected in the serum of YAPKO animals. YAP-interacting TEA domain transcription factor (TEAD) family members bound promoter regions of different secreted factors and may contribute to a severe inflammatory response in mice with YAP-inactivation in HCs and BECs. Conclusions YAP inactivation causes severe liver damage in vivo and concomitant TAZ deletion does not enhance but moderately reduce this phenotype. Furthermore, we describe a new mechanism how YAP inactivation in HCs/BECs contributes to YAP-driven heterologous cell communication originating from NPCs.
2024-02-26 | GSE234260 | GEO
Project description:Uncontrolled Transforming growth factor-beta (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGFβ, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGFβ signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (TAZ/YAP), the TEAD family of transcription factors (TEAD1/2/3/4), or the TGFb signaling pathway (with SB-431542, an inhibitor of the TBRI recpeptor) in human MDA-MB-231-LM2 breast cancer cells treated with TGFβ1. Human MDA-MB-231-LM2-4 breast cancer cells were transfected with control siRNA, or siRNAs targeting TAZ/YAP or all four TEADs and were treated 24 hours later with 500pM TGFβ1 or 5mM SB-431542 for an additional 24 hours. Total RNA was isolated and twelve microarrays in total were performed, with each condition carried out three times on separate days. The Boston University Microarray Core generated the data using the Affymetrix Human Gene 1.0 St Array.
2014-04-02 | E-GEOD-56445 | biostudies-arrayexpress