Jagged1 regulates miRNA expression profile
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56801 | GEO | 2014/05/30
SECONDARY ACCESSION(S): PRJNA244629
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA expression profiles of HMECs treated with 40mM Jagged1 (JAG1) or the control peptide for 1 day Genome-wide miRNA PCR array analysis was performed using human miRNA PCR arrays (MIHS216Z, SABiosceinces) acccording to the manufacturer's instructions
2014-05-30 | E-GEOD-56801 | biostudies-arrayexpress
Project description:Proinflammatory activation of endothelial cells leads to recruitment of leukocytes by upregulation of adhesion molecules and presentation of chemoattractants. In response to such activation there is also a strong shift in the endothelial expression of Notch ligands, with downregulation of Dll4 and a upregulation of JAG1. To assess whether Jagged1 would affect the endothelial activation profile, we suppressed JAG1 expression during IL-1β-induced activation by means of siRNA and performed a genome-wide transcriptome analysis. Our results show for the first time that Jagged1 modulates the transcription profile of activated endothelial cells and describe data that imply a role for Jagged1 in sharpening the inflammatory profile of the vasculature, giving it an edge towards leukocyte recruitment. These findings imply that Jagged1 might be a potential therapeutic target to attenuate inflammation and reduce tissue damage in inflammatory diseases.
2018-08-29 | GSE39180 | GEO
Project description:Vascular morphogenesis requires a delicate gradient of Notch signaling that is controlled, at least in part, by the distribution of ligands (Dll4 and Jagged1). How jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here we showed that Jag1 mRNA is a direct target of zinc finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we found robustly induced by VEGF. Endothelial cells lacking ZFP36 displayed high levels of JAG1 and increased angiogenic sprouting in vitro. Similarly, mice lackingZfp36in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front altered NOTCH1 signaling, increasing the number of tip cells; a phenotype that was rescued by imposing haploinsufficiency ofJag1. Our findings reveal an important feedforward loop, whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis.
2023-12-04 | GSE235462 | GEO
Project description:Objective Notch signaling is re-activated in β cells from obese mice, and is causal to β cell dysfunction. Notch activity is determined in part by expression of transmembrane ligand availability in a neighboring cell. We hypothesized that β cell expression of Jagged1 determines the maladaptive Notch response and resultant β cell dysfunction in obese mice. Methods We assessed expression of Notch pathway components in diet-induced obese (DIO) or leptin receptor-deficient (db/db) mice, and performed single cell RNA sequencing (scRNAseq) in islets from patients with and without type 2 diabetes (T2D). We generated and performed glucose tolerance testing in inducible, β cell-specific Jagged1 gain-of- and loss-of-function mice. We also tested effects of monoclonal neutralizing antibodies to Jagged1 in glucose-stimulated insulin secretion (GSIS) assays in isolated islets. Results Jag1 was the only Notch ligand that tracked with increased Notch activity in DIO and db/db mice. Consistently, JAG1 tracked with Notch activity in metabolically inflexible β cells enriched in patients with T2D. Neutralizing antibodies to block Jagged1 in islets isolated from DIO and db/db mice potentiated GSIS ex vivo. To demonstrate if β cell Jagged1 is sufficient to cause glucose tolerance in vivo, we generated inducible β cell-specific Jag1 transgenic mice (β-Jag1TG), which showed impaired glucose intolerance due to reduced GSIS. However, β cell-specific Jagged1 loss-of-function (β-Jag1KO) did not protect against HFD-induced insulin secretory defects or glucose intolerance. Conclusions Jagged1 is increased in islets from obese mice and in patients with T2D, and neutralizing Jagged1 antibodies lead to improved GSIS, suggesting that inhibition of Jagged1-Notch signaling may have therapeutic benefit. However, genetic loss-of-function experiments suggest that β cells are not a likely source of the Jagged1 signal.
2024-02-23 | GSE249170 | GEO
Project description:Inner ear cochlear supporting cells (SCs) are highly specialized glia-like cells that structurally and functionally support neighboring mechano-sensory hair cells. Despite their importance for proper auditory function, little is known about the molecular mechanisms that control their development. In this study we investigated the function of the Notch ligand Jagged1 (Jag1) in cochlear SC differentiation and maintenance. To address the function of Jag1 in the differentiation of SCs, we conditionally deleted Jag1 in stage E14.5 SC precursors using the recently established Sox2-CreER/+ and Jag1 fx/fx mouse lines. Analysis of stage P0 Jag1 mutant and control animals revealed that Hensen cells, a highly specialized SC-subtype located at the lateral edge of the auditory sensory epithelium, failed to form in the absence of Jag1. Other SC-subtypes did form in the absence of Jag1, however, their morphology and cellular arrangement was abnormal and SC-subtype specific genes and genes associated with mitochondrial function and protein synthesis were significantly reduced, indicating global defects in SC differentiation and SC homeostasis.
2020-12-16 | GSE148009 | GEO
Project description:Notch signaling is an evolutionarily conserved pathway that functions via direct cell-cell contact. The Notch ligand Jagged1 (Jag1) has been extensively studied in vascular development, particularly for its role in smooth muscle cell maturation. Endothelial cell-expressed Jag1 is essential for blood vessel formation by signaling to nascent vascular smooth muscle cells and promoting their differentiation. Given the established importance of Jag1 in endothelial cell/smooth muscle crosstalk during development, we sought to determine the extent of this communication in the adult vasculature for blood vessel function and homeostasis.
2022-08-01 | GSE209736 | GEO
Project description:Treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and expensive. Current reconstructive methods include surgical correction of injuries, short-term bone stabilization, and long-term use of bone grafting solutions, including implantation of (i) allografts which are prone to implant failure or infection, (ii) autografts which are limited in supply. Current bone regenerative approaches have consistently relied on BMP-2 application with or without addition of stem cells. BMP2 treatment can lead to severe bony overgrowth or uncontrolled inflammation, which can accelerate further bone loss. Bone marrow-derived mesenchymal stem cell-based treatments, which do not have the side effects of BMP2, are not currently FDA approved, and are time and resource intensive. There is a critical need for novel bone regenerative therapies to treat CF bone loss that have minimal side effects, are easily available, and are affordable. In this study we investigated novel bone regenerative therapies downstream of JAGGED1 (JAG1). We previously demonstrated that JAG1 induces murine cranial neural crest (CNC) cells towards osteoblast commitment via a NOTCH non-canonical pathway involving JAK2-STAT5 (1) and that JAG1 delivery with CNC cells elicits bone regeneration in vivo. In this study, we hypothesized that delivery of JAG1 and induction of its downstream NOTCH non-canonical signaling in pediatric human osteoblasts constitute an effective bone regenerative treatment in an in vivo murine bone loss model of a critically-sized cranial defect. Using this CF defect model in vivo, we delivered JAG1 with pediatric human bone-derived osteoblast-like (HBO) cells to demonstrate the osteo-inductive properties of JAG1 in human cells and in vitro we utilized the HBO cells to identify the downstream non-canonical JAG1 signaling intermediates as effective bone regenerative treatments. In vitro, we identified an important mechanism by which JAG1 induces pediatric osteoblast commitment and bone formation involving the phosphorylation of p70 S6K. This discovery enables potential new treatment avenues involving the delivery of tethered JAG1 and the downstream activators of p70 S6K as powerful bone regenerative therapies in pediatric CF bone loss.
2024-10-11 | GSE274096 | GEO
Project description:Transcriptional profiling of MC3T3-E1 osteoblasts that were flow cytometry-separated from cocultures with control or Jagged1-overexpressing tumor cells and treated with either DMSO control or 1μM MRK-003 (gamma-secretase inhibitor). One cell line (MC3T3-E1) cells: four different experimental conditions: cultured with (1) control tumor cells + DMSO; (2) Jagged1-overexpressing tumor cells + DMSO; (3) control tumor cells + MRK-003; (4) Jagged1-overexpressing tumor cells + MRK-003. Each experiment has two biological replicates. Total, 8 samples.
2010-08-15 | E-GEOD-20517 | biostudies-arrayexpress
Project description:The present study aimed to determine mRNA expression profilling of indirect immobilized Jagged1 treated human dental pulp cells. Human dental pulp cells were seeded on indirect immobilized Jagged1 surface for 24 h. Cells on hFc immobilized surface was employed as the control. RNA sequencing was performed using NextSeq500, Illumina. Data were processed on FastQC and FastQ Toolkit and subsequently mapped with Homo sapiens hg38 using TopHat2. Mapped data were processed through Cufflink2 and Cuffdiff2. Results demonstrated 1,465 differentially expressed genes in Jagged1 treated cells compared with the control. Enriched pathway analysis revealed that Jagged1 treated cells upregulated genes mainly involved in extracellular matrix organization, disease, and signal transduction categories. However, genes related to cell cycle, DNA replication and DNA repair categories were downregulated. In conclusion, Jagged1 activates Notch signaling and regulates cell cycle pathway in hDPs.
2017-04-04 | GSE94989 | GEO
Project description:Breast cancer is one of the leading causes of cancer-related mortality in women. NOTCH signaling is a well conserved pathway which not only plays critical roles in normal development, but also in cancer progression. One of the Notch ligand, JAGGED1 is overexpressed in about 30% of breast cancer patients. However, the role of JAGGED1 in breast tumorigenesis has not been rigorously examined. By utilizing genetic engineered mouse models of mammary specific Jagged1 expression or knockout, we discover that Jagged1 promotes tumorigenesis in multiple spontaneous mammary tumor models. Jagged1 expression leads to increased infiltration of tumor associated macrophages and decreased presentation of T cells within tumor microenvironment. Depletion of macrophages or T cells by neutralizing antibodies diminishes the tumor-promoting effect caused by Jagged1. Mechanistically, Jagged1 activates Notch signaling in tumor cells, leads to increased expression and secretion of multiple cytokines, including IL-6 and WISP. These cytokines help recruit macrophages into the tumor microenvironment. Macrophages crosstalk with infiltrated T cells and inhibit their cytotoxic killing on tumor cells. In triple negative breast cancer patient samples, high expression level of JAGGED1 correlates with increased macrophage infiltration and decreased T cell infiltration within tumor tissues. JAGGED1 also promotes tumor progression in several other solid cancer types, including melanoma, and colon cancer in a T cell dependent manner. Co-administration of immune checkpoint inhibitor, PD-1 antibody with gamma-secretase inhibitor (GSI) significantly inhibits tumor growth. These findings identify a unique oncogenic crosstalk between tumor derived JAGGED1, Macrophages, and T cells to promote tumor progression.
2022-03-08 | GSE161769 | GEO