Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis

ABSTRACT: The bivalent domain at promoter region is a unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of bivalent domains in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA stimulation, we discovered that bivalent domains are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The bivalent domains responsive to VEGFA have more permissive chromatin environment comparing to other bivalent domains. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrated a novel dual function of bivalent domains in endothelial cells to control VEGF responsiveness and angiogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139077 | GEO | 2020/10/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis

Project description:Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis

| PRJNA578281 | ENA

flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response

Project description:VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years; however, many challenges remain. Here we investigate a different approach to augmenting VEGFA bioavailability, one that achieves more physiological VEGFA concentrations by deleting VEGFR1/FLT1, a VEGFA decoy receptor. We find that, following cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring. Suppressing Vegfa signaling in flt1 mutants abrogates the beneficial effects of flt1 deletion. Transcriptomic analyses of cryoinjured flt1 mutant hearts revealed enhanced endothelial MAPK/ERK signaling and downregulation of the transcription factor gene egr3. Using genetic tools, we observe egr3 upregulation in the regenerating endocardium and find that Egr3 promotes myofibroblast differentiation. These data suggest that with enhanced VEGFA bioavailability, the cardiac endothelium limits myofibroblast differentiation via egr3 downregulation, thereby providing a more permissive microenvironment for cardiomyocyte replenishment after injury.

2024-11-12 | GSE264406 | GEO

Etv6-dependent positive and negative gene regulatory network controls vegfa expression in vivo [ChIP-seq]

Project description:VEGFA signaling is crucial for physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VegfA have been uncovered, vegfa transcriptional regulation in vivo is unclear. Here, we show that ETS transcription factor Etv6 positively regulates vegfa expression during blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits expression of vegfa repressor foxo3. Surprisingly, it also directly activates expression of vegfa activator klf4. Finally, it indirectly binds to vegfa promoter by the recruiment of Klf4. Thus, our work uncovers a dual function for Etv6, as both a transcriptional repressor and activator, in controlling a major signaling pathway.

2019-01-16 | GSE115224 | GEO

Etv6-dependent positive and negative gene regulatory network controls vegfa expression in vivo [RNA-seq]

2019-01-16 | GSE115220 | GEO

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [scRNA-seq]

Project description:The lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show that Vascular endothelial growth factor A (Vegfa) from the epithelium specifies a distinct endothelial cell (EC) population in the postnatal mouse lung. Vegfa is predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single cell RNA-seq identified 15~20% lung ECs as transcriptionally distinct and marked by Carbonic anhydrase 4 (Car4), which are specifically lost upon epithelial Vegfa deletion. Car4 ECs, unlike bulk ECs, have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without any intervening pericytes. Without Car4 ECs, the alveolar space is aberrantly enlarged despite the normal appearance of myofibroblasts. Lung Car4 ECs and retina tip ECs have common and distinct transcriptional profiles. These findings support a signaling role of AT1 cells and shed light on alveologenesis.

2020-01-01 | GSE124323 | GEO

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [bulk RNA-seq]

2020-01-01 | GSE124324 | GEO

LncRNA SPRY4-IT1 Facilitates Cell Proliferation and Angiogenesis of Glioma by the miR-101-3p/EZH2/VEGFA Signaling Axis

Project description:SPRY4-IT1 (SPRY4 intronic transcript 1) is a long non-coding RNA (lncRNA) that was identified as a novel oncogene in various human cancers, including glioma. However, its function and the further mechanism in glioma remain largely unclear. Here, we aimed to investigate the role of SPRY4-IT1 in the development of glioma and its underlying molecular mechanism. We identify that SPRY4-IT1 is overexpressed in patients with glioma from the TCGA database and own cohort, and correlated with poor prognosis of patients. Then, loss of function and gain of function cell model were established by transfected with siRNA and pcDNA3.1 plasmid. SPRY4-IT1 promotes glioma cells proliferation by Cell Count Kit 8 assays and EdU assay in vitro, and xenograft tumor assays in vivo. RNA sequence was performed to compare the transcriptomes of U87 siSPRY4-IT1-NC and U87 siSPRY4-IT1 cells, and Gene Ontology (GO) enrichment analysis indicated angiogenesis is significantly enriched. HUVEC tube forming assays and Chick Embryo Chorioallantoic Membrane (CAM) assays confirmed that SPRY4-IT1 can induce angiogenesis of glioma in vitro and in vivo. Mechanistically, we identify that SPRY4-IT1 upregulates EZH2 expression by sponge miR-101-3p to induce VEGFA expression in glioma cells. Moreover, SPRY4-IT1 activates VEGFR2/AKT/ERK1/2 pathway in HUVECs by glioma cell-mediated. Rescue experiments were performed by co-transfected with SPRY4-IT1 and EZH2 overexpression plasmid in glioma cells, and confirmed that SPRY4-IT1 promotes cell proliferation and angiogenesis of glioma by miR-101-3p/EZH2/VEGFA signaling axis. Taken together, our studies clarify that SPRY4-IT1 upregulates EZH2 to induce VEGFA by sponge miR-101-3p to achieve cell proliferation and angiogenesis in glioma. Thus, these findings have provided insights into the prognosis prediction and therapeutic target of glioma.

2022-06-30 | GSE189462 | GEO

Molecular analysis of endothelial and immune cells after anti-angiogenic cancer immunotherapy

Project description:Organism: Mus musculus Experiment type: Gene expression profiling by high throughput sequencing Summary: Pathological angiogenesis is a hallmark of cancer and therapeutic target. Vascular-endothelial growth factor-A (VEGFA) and angiopoietin-2 (ANGPT2/ANG2) sustain tumor angiogenesis and limit anti-tumor immunity. We show that combined ANGPT2 and VEGFA blockade by mono-specific antibodies (LC06 + B20) or a bi-specific antibody (A2V) provides synergistic anti-tumoral benefits in both transgenic and transplant tumor models. We further show that that combination of agonistic anti-CD40 or blocking anti-PD1 antibodies with ANGPT2/VEGFA blockade improves therapeutic response and induces pleiotropic immune mechanisms that facilitate tumor control.

2017-04-26 | GSE94920 | GEO

Cas13bt3 knockdown of VEGFA mRNA in retinal organoid [scRNA-Seq]

Project description:Purpose: We report expression of a new Cas13 enzyme in retinal cells and evaluate its efficacy in targeting the VEGFA mRNA to establish safety and efficacy of the enzyme got anti-VEGFA therapy. Methods: Three retinal organoids were cultured and treated, (1) Untreated, (2) AAV2.7m8.Cas13bt3.VEGFA.sgRNA, (3) AAV2.7m8.Cas13bt3.NTsgRNA. Single-cell RNA sequencing was performed to determine expression of Cas13bt3 across retinal cell types, and the corresponding VEGFA mRNA expression. Results: All retinal cell showed observable transduction and RPE cells were found most susceptible to infection, while bipolar cells had the least infection rate. Significant silencing of VEGFA was observed in RPE cells. Conclusions: AAV2.7m8 can be used for retina-wide transduction, and Cas13bt3 may be a potential new tool for control of VEGFA.

2024-03-01 | GSE259219 | GEO

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

Project description:Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

| PRJNA511606 | ENA