Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-50059
PROVIDER: PRJNA215899 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Endothelin2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis
2015-07-27 | E-GEOD-50059 | ExpressionAtlas
Project description:Endothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor. Z/Edn2 females were crossed to Six3-Cre; Six3-Cre males. Postnatal P8 pups were genotyped for the Z/Edn2 allele by detection of Laz-Z activity in tail clips. Retinas from 2 - 3 pups were pooled for each data point.
2014-01-01 | E-GEOD-50059 | biostudies-arrayexpress
Project description:Endothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor.
2014-01-01 | GSE50059 | GEO
Project description:Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here we show that diving tip cells invading the neuroretina (D-tip cells) are distinct from tip cells guiding the superficial retinal vascular plexus (S-tip cells). D-tip cells have a unique transcriptional signature, including high TGFβ signaling, and acquire blood-retina barrier properties. Endothelial deletion of TGFβ receptor I (Alk5) inhibits D-tip cell identity acquisition and deep vascular plexus formation. Loss of endothelial ALK5, but not of the canonical SMAD effectors, leads to aberrant contractile pericyte differentiation, and hemorrhagic vascular malformations. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that noncanonical-TGFβ signaling could improve retinal revascularization and neural function in ischemic retinopathy.
2021-07-16 | GSE175895 | GEO
Project description:Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of the vast crosstalk and compensatory mechanisms. Based on proteomic profiling of angiogenic endothelial components, here we report βIV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial specific βIV-spectrin promotes embryonic lethality in mice due to hypervascularization and hemorrhagic defects whereas neonatal depletion yields higher vascular density and tip cell populations in developing retina. During sprouting, βIV-spectrin expresses in stalk cells to inhibit their tip cell potential by enhancing VEGFR2 turnover in a manner independent of most cell-fate determining mechanisms. Rather, βIV-spectrin recruits CaMKII to the plasma membrane to directly phosphorylate VEGFR2 at Ser984, a previously undefined phosphoregulatory site that strongly induces VEGFR2 internalization and degradation. These findings support a distinct spectrin-based mechanism of tip-stalk cell specification during vascular development.
2022-02-04 | PXD026618 | Pride
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. Identification of endothelial-expressed microRNA from FACS-isolated zebrafish endothelial cells.
2012-02-28 | E-GEOD-35078 | biostudies-arrayexpress
Project description:<p>The retina is a notable tissue with high metabolic needs which relies on specialized vascular networks to protect the neural retina while maintaining constant supplies of oxygen, nutrients and dietary essential fatty acids. Here we analyzed the lipidome of the mouse retina under healthy and pathological angiogenesis using the oxygen-induced retinopathy model. By matching lipid profiles to changes in mRNA transcriptome, we identified a lipid signature showing that pathological angiogenesis leads to intense lipid remodeling favoring pathways for neutral lipid synthesis, cholesterol import/export and lipid droplet formation. Noteworthy, it also shows profound changes in pathways for long-chain fatty acid production, vital for retina homeostasis. The net result is accumulation of large quantities of mead acid, a marker of essential fatty acid deficiency, and a potential marker for retinopathy severity. Thus, our lipid signature might contribute to better understand diseases of the retina that lead to vision impairment or blindness.</p>
2023-05-09 | MTBLS6965 | MetaboLights
Project description:The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis. Four HUVEC donors were FACS-sorted by CD34 and divided in CD34-positive and CD34-negative fractions.
2012-01-05 | E-GEOD-34850 | biostudies-arrayexpress
Project description:The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.
2012-01-05 | GSE34850 | GEO
Project description:The development of the vertebrate vascular system is mediated by both genetic patterning of vessels and by angiogenic sprouting in response to hypoxia. Both of these processes depend on the detection of environmental guidance cues by endothelial cells. A specialized subtype of endothelial cell known as the tip cell is believed to be involved in the detection and response to these cues, but the molecular signaling pathways utilized by tip cells to mediate tissue vascularization remain largely uncharacterized. To identify genes critical to tip cell function, we have developed a method to isolate them using laser capture microdissection, permitting comparison of RNA extracted from endothelial tip cells to that of endothelial stalk cells using microarray analysis. Genes enriched in tip cells include ESM-1, Angiopoietin-2, and SLP-76. CXCR4, a receptor for the chemokine SDF-1, was also identified as a tip cell-enriched gene, and we provide evidence for a novel role for this receptor in mediating tip cell morphology and vascular patterning in the neonatal retina.
2010-03-17 | GSE19284 | GEO