Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-221 is required for endothelial tip cell behaviors during vascular development

ABSTRACT: Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin-dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis. Identification of endothelial-expressed microRNA from FACS-isolated zebrafish endothelial cells.

ORGANISM(S): Danio rerio

SUBMITTER: Abirami Lakshmanan

PROVIDER: E-GEOD-35078 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

miR-221 is required for endothelial tip cell behaviors during vascular development.

Nicoli Stefania S Knyphausen Carl-Philipp CP Zhu Lihua J LJ Lakshmanan Abirami A Lawson Nathan D ND

Developmental cell 20120201 2

Angiogenesis requires coordination of distinct cell behaviors between tip and stalk cells. Although this process is governed by regulatory interactions between the vascular endothelial growth factor (Vegf) and Notch signaling pathways, little is known about the potential role of microRNAs. Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 rece ...[more]

PMID: 22340502

Similar Datasets

miR-221 is required for endothelial tip cell behaviors during vascular development

Project description:Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin-dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis.

2012-02-28 | GSE35078 | GEO

MicroRNA expression in HMVECs: control vs. VEGF-treated vs. PEDF/VEGF-treated

Project description:MicroRNA expression profiling of human microvascular endothelial cells (HMVECs) treated with either vascular endothelial growth factor (VEGF) only or in combination with the natural angiogenesis inhibitor pigment epithelial-derived factor (PEDF). Originally we were interested in the microRNA-mediated regulation of angiogenesis by the endogenous anti-angiogenic PEDF. To identify the microRNAs involved in PEDF signaling in activated endothelial cells, we compared the levels of microRNAs in non-treated microvascular endothelial cells, cells treated with VEGF, and cells treated with a combination of VEGF and PEDF. After treatment, total RNA content was isolated and sent for analysis to LC Sciences, LLC. They performed expression profiling and completed statistical analysis, based on which we confirmed the regulation of one of the microRNAs, mir-27b. In the following experiments, we identified the targets of mir-27b relevant for angiogenesis and confirmed our findings in zebrafish and mouse models. The manuscript describes the key role of mir-27b in determination of the endothelial tip cell fate and venous differentiation by regulating Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2). Three-condition experiment: untreated (control) HMVECs vs. VEGF-treated HMVECs vs. PEDF/VEGF-treated HMVECs.

2011-12-31 | E-GEOD-34735 | biostudies-arrayexpress

MicroRNA expression in HMVECs: control vs. VEGF-treated vs. PEDF/VEGF-treated

2011-12-31 | GSE34735 | GEO

Pro-angiogenic transcriptome of zebrafish endothelial cells

Project description:To identify previously unknown determinants of endothelial cell sprouting, we defined and exploited a pharmacological strategy for the manipulation of angiogenic cell behavior in vivo. Whereas high vascular endothelial growth factor receptor (Vegfr) signaling is known to promote tip cell (TC) specification, activation of the Notch receptor via its ligand Delta-like 4 (Dll4) represses the TC phenotype to promote stalk cell (SC) fate. Conversely, suppression of Notch activity upon antagonistic interaction with its ligand Jagged1 pro- motes TC formation. Hence, specification of TCs involves tight spatiotemporal control of Vegfr/Notch signaling. Consequently, we hypothesized that the pharmacological manipulation of Vegfr/Notch signaling selectively during zebrafish intersegmental vessel (ISV) angiogenesis would enable the precise control of angiogenic EC behavior and sprouting- associated gene expression in vivo. For more information, see Herbert et al., 2012, PMID 22921365.

2019-05-09 | GSE130889 | GEO

Interactions of melanoma cells with distal keratinocytes trigger metastasis via Notch signaling inhibition of MITF

Project description:The most critical stage in initiation of melanoma metastasis is the radial to vertical growth transition, yet the triggers of this transition remain elusive. We introduce a novel perspective, suggesting that the microenvironment drives melanoma metastasis independently of mutation acquisition. Here we examined the changes in microenvironment that occur during melanoma radial growth. We show that direct contact of melanoma cells with the remote epidermal layer triggers vertical invasion via Notch signaling activation, the latter serving to inhibit MITF function. Briefly, within the native Notch ligand-free microenvironment, MITF, the melanocyte lineage master regulator, binds and represses miR-222/221 promoter in an RBPJK-dependent manner. However, when radial growth brings melanoma cells into contact with distal differentiated keratinocytes that express Notch ligands, the activated Notch intracellular domain impairs MITF binding to miR-222/221 promoter. This de-repression of miR-222/221 expression triggers initiation of invasion. Our findings may direct novel prevention opportunities via targeting specific microenvironment. Two replicates of Notch-activated cells that were seeded on Delta-like-1 (DLL1) (2 ng/µl ) coated plates were compared to two replicates of cells without Notch activation. The goal of this experiment is to evaluate the changes of miRs expression in melanoma cells upon Notch signaling activation.

2015-07-30 | E-GEOD-69403 | biostudies-arrayexpress

Proteomic analysis of primary human microvascular endothelial cells (HMVECs) stimulated for 24â€‰h with either 50 ï�g/mL recombinant Fibrillin-1 C-terminal fragment or 25â€‰ng/ml VEGF-A compared to unstimulated cells.

Project description:Mutations in the fibrillin-1 gene result in cardiovascular, ocular, and skeletal abnormalities in Marfan syndrome. Here we show that a fibrillin-1 mutation also alters the neovessel formation. In the mouse retina vascularization model, fibrillin-1 is detected at the basement membrane underlying the angiogenic front and around arterioles. In Fbn1C1041G/+ mice, a model of Marfan disease, the microvasculature is altered at these sites. At the front, endothelial tip-cell sprouting and branching are decreased, and we show that mutant fibrillin-1 delays angiogenesis by affecting Notch signalling. Supplying the growing vasculature of Fbn1C1041G/+ mice with a C-terminal fragment of fibrillin-1 corrects all defects. In vitro, the C-terminal fragment of fibrillin-1 also displays pro-angiogenic activities on microvascular endothelial cell. Our data establish that fibrillin-1 performs essential functions in microvessel formation and integrity and that mutant fibrillin-1-induced defects can be rescued pharmacologically.

2023-05-31 | PXD029834 | Pride

Interactions of melanoma cells with distal keratinocytes trigger metastasis via Notch signaling inhibition of MITF

2015-07-30 | GSE69403 | GEO

Danio rerio

Project description:miR-221 is required for endothelial tip cell behaviors during vascular development

| PRJNA150927 | ENA

Identification of the RNA-bound proteome in endothelial cells

Project description:Most new blood vessels emerge through sprouting angiogenesis, an intricate biological process that entails the coordinated migration of groups of endothelial cells branching from parental vessels. Critical guidance cues such as the Vascular Endothelial Growth Factor secreted by the surrounding tissues regulate the molecular and cellular responses triggered during angiogenesis. Similarly to other collective cell migration systems, endothelial cells within sprouting vessels are hierarchically organised into leader tip cells and follower stalk cells. Endothelial tip cells are highly polarised, exhibiting a leading edge that extends filopodia-containing protrusions and that interacts with the extracellular matrix, whilst their rear engages in cell-to-cell contacts with stalk cells. Polarisation of cytoplasmic components contributes to dynamic membrane remodelling phenomena that are constrained to the cell-leading front during migration. Amongst other factors, asymmetric distribution of mRNA is a well-established and crucial determinant of cell polarity. The active transport of transcripts is mediated by mRNA-binding proteins (mRBPs). Subcellular distribution of transcript messages results in restricted synthesis of the proteins they encode to particular compartments within the cell. This mode of post-transcriptional control of gene expression contributes to rapid and localised cellular responses to dynamic environmental stimuli with implications in development and disease. Although the involvement of RNA interacting proteins in angiogenesis has been previously reported, whether mRBPs play a role in asymmetric transcript localisation crucial for endothelial cell migration is yet to be fully explored.

2024-03-28 | PXD046994 | Pride

MicroRNA profiling of human hepatocellular carcinoma samples shows miR-221 overexpression contributes to liver tumorigenesis

Project description:We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93,miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most upregulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells.

2009-12-08 | E-TABM-866 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data