Gene expression of APJ deficient endothelial cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66073 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA275829
REPOSITORIES: GEO
Similar Datasets
Project description:Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well-established, but control of parallel arterial-venous (A-V) alignment is unclear. We report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs. We used microarrays to detail the global programme of gene expression in endothelial cells that has relationship with the deficient of APJ. Endothelial cells were marked and isolated by Fluorescence-activated cell sorting in Trizol.
2016-07-03 | E-GEOD-66073 | biostudies-arrayexpress
Project description:Evaluation of microRNAs that are downstream of apelin/APJ signaling in the pulmonary artery endothelial cells. Triplicates per group, subjected to: 1) control siRNA, 2) apelin siRNA, 3) APJ siRNA, 4) apelin + APJ siRNA
2012-12-04 | E-GEOD-42343 | biostudies-arrayexpress
Project description:Evaluation of gene transcripts that are downstream of apelin/APJ and FoxO1 signaling in HUVECs
2017-10-02 | GSE67390 | GEO
Project description:Evaluation of gene transcripts that are downstream of apelin/APJ signaling in HUVECs Duplicates per group, subjected to: 1) control siRNA, 2) MEF2A and MEF2C siRNA, 3) G alpha 13 siRNA, and 4) apelin and APJ siRNA
2013-05-11 | E-GEOD-46825 | biostudies-arrayexpress
Project description:Evaluation of microRNAs that are downstream of apelin/APJ signaling in the pulmonary artery endothelial cells.
2012-12-04 | GSE42343 | GEO
Project description:Evaluation of gene transcripts that are downstream of apelin/APJ signaling in HUVECs
2013-05-11 | GSE46825 | GEO
Project description:Brain arteriovenous malformations (bAVM) are characterized by enlarged blood vessels, which direct blood through arteriovenous AV shunts, bypassing the artery-capillary-vein network and disrupting blood flow. Clinically, bAVM treatments are invasive and not routinely applicable. There is critical need to understand mechanisms of bAVM pathologies and develop pharmacological therapies. We used an in vivo mouse model of Rbpj-mediated bAVM, which develops pathologies in the early postnatal period and an siRNA in vitro system to knockdown RBPJ in human brain microvascular endothelial cells (ECs). To understand molecular events regulated by endothelial Rbpj, we conducted RNA-Seq and ChIP-Seq analyses from isolated brain ECs. Rbpj-deficient (mutant) brain ECs acquired abnormally rounded shape (with no change to cell area), altered basement membrane dynamics, and increased EC density along AV shunts, compared to controls, suggesting impaired remodeling of neonatal brain vasculature. Consistent with impaired EC dynamics, we found increased Cdc42 activity in isolated mutant ECs, suggesting that Rbpj regulates small GTPase-mediated cellular functions in brain ECs. siRNA treated, RBPJ-deficient human brain ECs displayed increased Cdc42 activity, disrupted cell polarity and focal adhesion properties, and impaired migration in vitro. RNA-Seq analysis from isolated brain ECs identified differentially expressed genes in mutants, including Apelin, which encodes a ligand for G protein-coupled receptor signaling known to influence small GTPase activity. ChIP-Seq analysis revealed chromatin loci occupied by Rbpj in brain ECs that corresponded to G-protein and Apelin signaling molecules. In vivo administration of a competitive peptide antagonist against the Apelin receptor (Aplnr/Apj) attenuated Cdc42 activity and restored EC morphology and AV connection diameter in Rbpj-mutant brain vessels. Conclusions: Our data suggest that endothelial Rbpj promotes rearrangement of brain ECs during cerebrovascular remodeling, through Apelin/Apj-mediated small GTPase activity, and prevents bAVM. By inhibiting Apelin/Apj signaling in vivo, we demonstrated pharmacological prevention of Rbpj mediated bAVM.
2023-02-01 | GSE223532 | GEO
Project description:Brain arteriovenous malformations (bAVM) are characterized by enlarged blood vessels, which direct blood through arteriovenous AV shunts, bypassing the artery-capillary-vein network and disrupting blood flow. Clinically, bAVM treatments are invasive and not routinely applicable. There is critical need to understand mechanisms of bAVM pathologies and develop pharmacological therapies. We used an in vivo mouse model of Rbpj-mediated bAVM, which develops pathologies in the early postnatal period and an siRNA in vitro system to knockdown RBPJ in human brain microvascular endothelial cells (ECs). To understand molecular events regulated by endothelial Rbpj, we conducted RNA-Seq and ChIP-Seq analyses from isolated brain ECs. Rbpj-deficient (mutant) brain ECs acquired abnormally rounded shape (with no change to cell area), altered basement membrane dynamics, and increased EC density along AV shunts, compared to controls, suggesting impaired remodeling of neonatal brain vasculature. Consistent with impaired EC dynamics, we found increased Cdc42 activity in isolated mutant ECs, suggesting that Rbpj regulates small GTPase-mediated cellular functions in brain ECs. siRNA treated, RBPJ-deficient human brain ECs displayed increased Cdc42 activity, disrupted cell polarity and focal adhesion properties, and impaired migration in vitro. RNA-Seq analysis from isolated brain ECs identified differentially expressed genes in mutants, including Apelin, which encodes a ligand for G protein-coupled receptor signaling known to influence small GTPase activity. ChIP-Seq analysis revealed chromatin loci occupied by Rbpj in brain ECs that corresponded to G-protein and Apelin signaling molecules. In vivo administration of a competitive peptide antagonist against the Apelin receptor (Aplnr/Apj) attenuated Cdc42 activity and restored EC morphology and AV connection diameter in Rbpj-mutant brain vessels. Conclusions: Our data suggest that endothelial Rbpj promotes rearrangement of brain ECs during cerebrovascular remodeling, through Apelin/Apj-mediated small GTPase activity, and prevents bAVM. By inhibiting Apelin/Apj signaling in vivo, we demonstrated pharmacological prevention of Rbpj mediated bAVM.
2023-02-01 | GSE223531 | GEO
Project description:The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly occurs in females who have either a partial or complete loss of one of their X chromosomes. Our understanding of the role granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. Here, we elevated GC differentiation efficiency up to the level of 80% differentiated cells from iPSCs. In our attempt to replicate the differentiation process of embryonic granulosa cells, we observed that specific genes—GATA4, FOXL2, AMHR2, CYP19A1, and FSH—were downregulated in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, dysregulation of the cell cycle was observed in TS-GCs. To reveal the endogenous defects in the TS-GCs, we conducted a comparison of the global transcriptome patterns between differentiated granulosa cells derived from iPSCs in both healthy and Turner syndrome groups. The apelin/APJ pathway displayed a differential between the healthy and TS groups. Supplementation of apelin ligands and activation of apelin/APJ downstream signals via Akt/PKB restored the cell cycle progression and marker gene expression. We hypothesize that during early embryonic development failures in apelin/APJ signaling in GCs in Turner syndrome patients leads to abnormalities in ovarian development and consequently to early loss of oocytes and infertility.
2024-11-20 | GSE271780 | GEO
Project description:The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The endothelial cells (ECs) that line the lumens of blood and lymphatic vessels play an integral role in the regional specialization of vascular structure and physiology. However, our understanding of EC diversity is limited. To explore EC specialization on a global scale, we used DNA microarrays to determine the expression profile of 53 cultured ECs. We found that ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the ECs of large vessels from microvascular ECs. We identified groups of genes characteristic of arterial and venous endothelium. Hey2, the human homologue of the zebrafish gene gridlock, was selectively expressed in arterial ECs and induced the expression of several arterial-specific genes. Several genes critical in the establishment of left/right asymmetry were expressed preferentially in venous ECs, suggesting coordination between vascular differentiation and body plan development. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues. A development or differentiation experiment design type assays events associated with development or differentiation or moving through a life cycle. Development applies to organism(s) acquiring a mature state, and differentiation applies to cells acquiring specialized functions. Using regression correlation
2005-12-20 | E-GEOD-3874 | biostudies-arrayexpress