Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA278875 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The sensory epithelium of the cochlea is a specialized structure responsible for the perception of sound. While much is understood about the development of the mechanosensory hair cells found within this epithelium, little is known about the development of the glial-like supporting cells. Here, we provide evidence that in addition to its well-characterized inhibitory function, canonical Notch signaling plays a positive, instructive role in the differentiation of supporting cells. Using γ-secretase inhibitor DAPT to acutely block canonical Notch signaling, we identified a cohort of Notch-regulated supporting cell-specific genes, with diverse functions in cell signaling, cell differentiation, neuronal innervation and synaptogenesis.
2016-02-01 | GSE67085 | GEO
Project description:Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance. We found HES5 to be strongly activated by Notch signaling. In vitro, HES5 reduced cell migration and clonogenicity and in vivo, HES5 inhibited MYC-dependent liver tumor formation. But together with AKT, HES5 increased liver tumor formation in a mouse model. HES5 directly binds to AKT and AKT expression leads to increase HES5 protein levels. Furthermore, HES5 exhibits a negative feed-back loop by inhibiting NOTCH1 and HES1 gene expression. In contrast, HES5-R31G appears to be non-functional possibly by loss of nuclear translocation
| EGAS00001003329 | EGA
Project description:Sivakumar2011 - Notch Signaling Pathway
Notch is a transmembrane receptor that mediates local cell-cell communication and coordinates a signaling cascade. It plays a key role in modulating cell fate decisions throughout the development of invertebrate and vertebrate species and the misregulation leads to a number of human diseases.
References:
Notch signaling: from the outside in.
Notch signaling in hematopoiesis and early lymphocyte development.
An overview of the Notch signalling pathway.
Notch and cancer: best to avoid the ups and downs.
Notch signaling: control of cell communication and cell fate.
This model is described in the article:
A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S.
Omics: a Journal of Integrative Biology. 2011; 15(10):729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs.
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2024-09-02 | BIOMD0000000396 | BioModels
Project description:COUP-TFII plays a critical role in angiogenesis during development. It has also been shown to suppress Notch signaling pathway to confer vein identity. However, the downstream targets and the mechanism mediate COUP-TFII function to regulate these processes remain elusive. To identify the downstream targets and the mechanism by which COUP-TFII regulates agiogenesis and vein specification, we knocked down COUP-TFII in HUVEC cells using COUP-TFII specific siRNA and used microarray analysis to identify downstream targets. Interestingly, we found the expression of many genes in the cell cycle pathway and Notch signaling pathway are significantly altered in the COUP-TFII depleted cells. HUVEC Cells were transfected with siRNA (Control or COUP-TFII siRNA) duplexes (50 nM) and total RNA was isolated 48 hours later.
2011-10-27 | E-GEOD-33301 | biostudies-arrayexpress
Project description:The ventricular wall of the heart is composed of trabeculated and compactlayers, which are separated by yet unknown processes during embryonic development. Notch signaling plays important roles in cardiac development. Mutations in Notch signaling components are related to human congenital heart diseases Two homologues, Numb and Numblike (Numbl), are expressed in mammals, which also act as inhibitors of Notch signaling Here we investigate the role of Notch2 and Numb/Numblike during myocardial trabeculation and compaction. The aim of the experiment is to analyze whether Numb/Numblike are involved in inhibition of Notch activity in the developing heart.
2013-01-17 | E-MEXP-3490 | biostudies-arrayexpress
Project description:The ventricular wall of the heart is composed of trabeculated and compactlayers, which are separated by yet unknown processes during embryonic development. Notch signaling plays important roles in cardiac development. Mutations in Notch signaling components are related to human congenital heart diseases Two homologues, Numb and Numblike (Numbl), are expressed in mammals, which also act as inhibitors of Notch signaling. Here we investigate the role of Notch2 and Numb/Numblike during myocardial trabeculation and compaction. The aim of the experiment is to analyze whether Numb/Numblike are involved in inhibition of Notch activity in the developing heart. Since Overexpression of N2ICD phenocoped Numb/Numblike mutants, we performed micoarray using total RNA from aMHC-Cre-mediated overexpression of N2ICD.
2013-04-09 | E-MEXP-3661 | biostudies-arrayexpress
Project description:<p>Splenic Marginal Zone Lymphoma (SMZL) is a B-cell malignancy of unknown pathogenesis and thus orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis of 8 paired tumor-normal DNAs from patients with SMZL, we show that the typical SMZL exome carries ~30 genetic alterations. Targeted resequencing of selected candidates in an extended panel of 40-117 samples revealed activating mutations of NOTCH2, a gene required for marginal-zone (MZ) development, as the most frequent and SMZL-specific lesion, accounting for approximately 20% of cases. Additional altered genes suggest that deregulation of signaling pathways normally involved in MZ development (NOTCH, NF-kappa B, and B-cell receptor) represents a critical event in SMZL pathogenesis. These findings have direct implications for the treatment of SMZL patients since drugs are available which can target NOTCH as well as other pathways deregulated in this disease.</p>
| phs000502 | dbGaP
Project description:Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance.
2019-10-31 | GSE121362 | GEO
Project description:Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival by interacting with Notch ligands on adjacent cells. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remain unclear. In this report we demonstrate that the Notch ligand Dll1 on CD4+ T cells transduces signals required for the maintenance of activated CD4+ T cells without affecting Notch signaling in the same cells. T cell-specific Dll1-deficient (Dll1-/-) mice did not show any defect in T cell development in thymus or spleen. Co-transfer of CD4+ T cells from Dll1-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1-/- mice compared with control cells. Dll1-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data highlight Dll1 as an independent regulator of Notch-signaling for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses The mRNA expression in activated CD4+ T cells from mouse was obtained by DNA microarray analysis. These mRNA expression was compared.
2016-01-09 | E-GEOD-76693 | biostudies-arrayexpress
Project description:Loss of function studies have shown that transcription factor T cell factor-1 (TCF1), encoded by the Tcf7 gene, is essential for T cell development in the thymus. We discovered that the Tcf7 expression level is regulated by E box DNA binding proteins, independent of Notch, and regulates ab and gd T cell development. Systematic interrogation of the five E-protein binding elements (EPE1-5) in the Tcf7 enhancer region showed lineage-specific utilization. Specifically, loss-of-function analysis revealed that only EPE3 plays a critical role in supporting ab T cell development, while EPE1, 3 and 5 regulate gd T cell maturation and functional cell fate decision. The importance of EPE3 in supporting both lineages may stem from its unique capacity to interact with the Tcf7 transcriptional start site. Together these studies demonstrate that the precise dosage of TCF1 expression mediated by distinct EPEs generates a balanced output of T cells from the thymus.
2024-10-18 | GSE270094 | GEO