Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome
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ABSTRACT:
PROVIDER: PRJNA1133075 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29751567_1.fastq.gz | Fastqsanger.gz | |||
| SRR29751567_2.fastq.gz | Fastqsanger.gz | |||
| SRR29751568_1.fastq.gz | Fastqsanger.gz | |||
| SRR29751568_2.fastq.gz | Fastqsanger.gz | |||
| SRR29751569_1.fastq.gz | Fastqsanger.gz |
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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: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
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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
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Project description:Evaluation of gene transcripts that are downstream of apelin/APJ and FoxO1 signaling in HUVECs
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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
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Project description:Apelin is a hormone secreted primarily by white adipose tissue. Recent studies have shown that adipokine and its receptor, APJ, are expressed in different reproductive tissues, including the ovary and uterus, which suggests that it may act as an important local regulator of reproductive functions. This study aimed to explore the influence of apelin on global gene expression in the porcine endometrium during early gestation, on days 15 to 16 of pregnancy (implantation period). We analysed samples obtained from 4 individuals (n=4). The tissue explants obtained from the uterine horns were divided into controls [without treatment] and apelin-13 (20 ng/mL) treated ones. In vitro tissue cultures were conducted for 24 hours.
2024-03-18 | E-MTAB-13773 | biostudies-arrayexpress
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: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:First, transcriptome analysis of purified CD31+ endothelial cells (ECs) from VEGF-treated sprouting embryoid bodies showed angiogenesis as the top affected category when Apelin is not present. In addition, loss of Apelin resulted in the modulation of pathways in ECs related to vasculogenesis, cell adhesion and response to hypoxia. Ingenuity Pathway Analysis (IPA) further identified VEGFR pathway as the main upstream regulator affected in endothelial cells, closely followed by the TGFβ1 and TNF pathways, all reduced in the absence of Apelin. The most inhibited genes from the VEGFR pathway in the absence of Apelin are angiogenesis-related genes. Second, transcriptome analysis of CD31+/CD105+ ECs sorted from Apelin wild-type and Apln-depleted tumors found a significant decrease in processes associated with endothelial cell proliferation and angiogenesis in ECs sorted out of Apelin-depleted tumors using IPA. Further, IPA predicted a decrease in the adhesion of granulocytes and upstream regulator analysis showed that proteins of the TGF-superfamily, Inhibin-βA and TGF-β1, as well as C/EBP-alpha, β-Catenin, ErbB2 and EGFR are predicted to be inhibited upstream regulators in ECs isolated from Apelin-depleted tumors.
2019-05-27 | GSE100293 | GEO