Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA150137 | ENA |
REPOSITORIES: ENA
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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 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: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: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
Project description:Angiogenic homeostasis is maintained by a balance between vascular endothelial growth factor (VEGF) and Notch signalling in endothelial cells (ECs). We screened for molecules that might mediate the coupling of VEGF signal transduction with down-regulation of Notch signalling, and identified B-cell chronic lymphocytic leukemia/lymphoma6-associated zinc finger protein (BAZF). BAZF was induced by VEGF-A in ECs to bind to the Notch signalling factor CBF1, and to promote the degradation of CBF1 through polyubiquitination in a CBF1-cullin3 (CUL3) E3 ligase complex. BAZF disruption in vivo decreased endothelial tip cell number and filopodia protrusion, and markedly abrogated vascular plexus formation in the mouse retina, overlapping the retinal phenotype seen in response to Notch activation. Further, impaired angiogenesis and capillary remodeling were observed in skin-wounded BAZF-/- mice. We therefore propose that BAZF supports angiogenic sprouting via BAZF-CUL3-based polyubiquitination-dependent degradation of CBF1 to down-regulate Notch signalling. Human umbilical vein endothelial cells were stimulated with recombinant human VEGF165 for 0, 1, 2, 6, 12, 24 and 48 hours.
2012-03-25 | E-GEOD-35171 | biostudies-arrayexpress
Project description:Angiogenesis-inhibitor (AI) drugs targeting vascular endothelial growth factor (VEGF) signalling to the endothelial cell (EC) are used to treat various cancers types. However, primary or secondary resistance to therapy is common. Clinical and pre-clinical studies suggest that other alternative pro-angiogenic factors are up-regulated after VEGF-pathway inhibition. Therefore, identification alternative pro-angiogenic pathway(s) is critical for the development of more effective anti-angiogenic therapy. Here we study the role of apelin as a pro-angiogenic G-protein coupled receptor (GPCR) ligand in tumor growth and angiogenesis. We applied single-cell RNA-sequencing to Mouse Lewis lung carcinoma (LLC1) or B16F10 mouse melanoma cell lines (1 X 106) implanted subcutaneously into the flanks of 12 weeks old Apln-/y or littermate control mice in combination with sunitinib or control (vehicle) treatment. We found apelin loss reduced angiogenic sprouting and tip cell marker gene expression in comparison to the sunitinib-alone treated mice and prevented EC tip cell differentiation.
2023-04-06 | E-MTAB-11663 | biostudies-arrayexpress
Project description:While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis. 7 samples analyzed, 2 replicates for NRP1+CD34+, 3 replicates for NRP1+CD34-
2013-12-14 | E-GEOD-44328 | biostudies-arrayexpress
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:While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis.
2013-12-14 | GSE44328 | GEO
Project description:We report a novel technique to reprogram human fibroblasts into endothelial and smooth muscle cells using partial iPSC reprogramming and chemically defined media. Using appropriate media conditions for differentiation of human pluripotent cells to CD34+ vascular progenitor cells, we show that temporary expression of pluripotent transcription factors and treatment with chemically-defined media, will induce differentiation of human fibroblasts to CD34+ vascular progenitor cells. Sorted CD34+ cells can then be directed to differentiate into vascular endothelial cells expressing a variety of smooth muscle markers. We have assessed the global DNA methylation (Illumina Infinium HD 450K DNA methylationBeadChips) and transcriptional (Illumina HT12v4 Gene Expression Bead Array) profiles of transdifferentiated endothelial cells and smooth muscle, human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) differentiated CD34+ angioblasts, hESCs, hiPSC, primary smooth muscle and primary human umbilical vein endothelial cells using microarrays.
2012-09-18 | E-GEOD-40909 | biostudies-arrayexpress