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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas

ABSTRACT: The Hippo signaling pathway has become recognized as a context-dependent regulator of cell proliferation, differentiation, and apoptosis in species ranging from Drosophila to human. In this study, we sought to understand whether Hippo signaling plays a role in pancreatic development and organ homeostasis. We analyzed mRNA from 5 samples each from control and DKO mouse pancreas using Affymetrix MouseGene 1.0 ST Array platfrom. Array data was processed by Affymetrix array computational tools.

ORGANISM(S): Mus musculus

SUBMITTER: Tao Gao

PROVIDER: E-GEOD-44298 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas

Project description:The Hippo signaling pathway has become recognized as a context-dependent regulator of cell proliferation, differentiation, and apoptosis in species ranging from Drosophila to human. In this study, we sought to understand whether Hippo signaling plays a role in pancreatic development and organ homeostasis.

2013-02-14 | GSE44298 | GEO

Hippo signaling regulates differentiation and maintenance in the exocrine pancreas.

Project description: Not available

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Transcriptional targets of Hippo signaling in mammalian cells

Project description:The Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth. We used microarrays to profile the gene expression patterns upon acute siRNA knockdown of Hippo pathway components in multiple mammalian cell lines and identified a set of genes representing immediate transcriptional targets of the Hippo/Yap signaling pathway. Three mammalian cell lines (HEK293T, HepG2, HaCaT) were transfected with scramble siRNA controls or siRNAs against NF2 and LATS2, two core components of the Hippo pathway, simultaneously. Total RNAs were harvested four days after transfection to reveal the gene expression pattern unsing microarry. YAP and TAZ siRNAs were also transfected along with NF2 and LATS2 siRNAs to identify YAP/TAZ-dependent transcriptional targets upon loss of NF2/LATS2.

2013-12-31 | E-GEOD-49384 | biostudies-arrayexpress

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Transcriptional targets of Hippo signaling in mammalian cells

2013-12-31 | GSE49384 | GEO

Genome-wide analysis of liver tissue mRNA expression from Pten-deficient and/or Sav1-deficient mice liver

Project description:To know the crosstalk between Hippo and AKT pathways in the liver metabolism, we generated liver-specific Pten (AKT signaling), Sav1 (Hippo signaling) and double-knockout mice and analysed the liver mRNA expression globally from 4groups (WT, Pten KO, Sav1 KO and Pten;Sav1 dKO).

2018-10-08 | GSE94797 | GEO

Hippo reprograms the transcriptional response to Ras signalling

Project description:Mutations that lead to hyperactivation of Ras signaling are hallmarks of carcinomas. During development, signaling via Ras mediates cell fate decisions and cellular differentiation without causing hyper-proliferation. What determines whether Ras activation leads to differentiation or proliferation remains unknown. Here we show that the Hippo pathway reprograms the cellular response to Ras signaling in Drosophila. While hyperactivation of Ras signaling alone promotes cellular differentiation, additional loss of Hippo signaling drives aggressive hyper-proliferation. Transcriptome analysis combined with ChIP-nexus confirmed that the magnitude and specificity of Ras target gene expression strongly depends on the activity status of the Hippo pathway. This is because Hippo signaling directly regulates the expression of two key downstream transcription factors of the Ras pathway: the ETS-domain transcription factor Pointed and the transcriptional repressor Capicua. Our results highlight how independent signaling pathways can impinge on each other at the level of transcription factors, thereby providing a safety mechanism to keep proliferation in check under normal developmental conditions.

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MST2 Methylation by PRMT5 Inhibits Hippo Signaling and Promotes Pancreatic Cancer Progression

Project description:As a classic tumor suppressor pathway, Hippo signaling axis is activated by various extra-pathway factors to regulate cell differentiation and organ development. However, recent studies have reported that the activation of Hippo signaling pathway may be more dependent on the autophosphorylation of its core kinase cassette. Here, we demonstrate that protein arginine methyltransferase 5 (PRMT5) is involved in inducing the inactivation of Hippo signaling pathway in pancreatic cancer. Our study shows that the initiator serine/threonine kinase 3 (STK3, also known as MST2) of Hippo signaling pathway can be symmetrically di-methylated at arginine-461 (R461) and arginine-467 (R467) in the SARAH domain by PRMT5, and the methylated MST2 suppresses its autophosphorylation and kinase activity by blocking the formation of homodimer, thereby inactivating Hippo signaling pathway in pancreatic cancer. Moreover, we also discover that the specific PRMT5 inhibitor GSK3326595 re-activates the dysregulated Hippo signaling pathway and inhibits the growth of human-derived pancreatic cancer xenografts in immunodeficient mice, which provides a theoretical foundation for the clinical application of PRMT5 inhibitor in pancreatic cancer.

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Semaphorin activates Hippo signaling to control cell growth

Project description:Semaphorin activates Hippo signaling to control cell growth

| PRJNA580522 | ENA

RNA sequencing reveals transcriptional changes after Hippo signaling activation in podocytes

Project description:Podocytes are crucial for the establishment and maintenance of the blood-urine filtration barrier in the glomeruli of the kidney. Activation of the Hippo signaling pathway in podocytes leads to the induction of apoptosis and could be linked to the pathogenesis of proteinuric diseases like focal segmental glomerulosclerosis (FSGS). To investigate the Hippo signaling controlled gene transcription, podocytes overexpressing LATS2, a core kinase of the Hippo pathway, were analyzed via RNA sequencing.

2018-08-30 | GSE114987 | GEO

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