Gene expression profiling of endothelial cell apoptosis induced by serum withdrawal
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE23067 | GEO | 2012/07/20
SECONDARY ACCESSION(S): PRJNA129877
REPOSITORIES: GEO
Similar Datasets
Project description:To understand the regulatory relationships among EC transcripts during apoptosis using serum withdrawal time series microarray data and use this to identify master regulators of endothelial cell apoptosis. In the study presenty here, HUVEC isolates from 10 different individuals were pooled. The extracted RNA was hybridised onto the microarray at different timepoints following treatment with serum withdrawal. The time course was replicated 3 times using three different pools of 10 HUVEC isolates.
2012-07-19 | E-GEOD-23067 | biostudies-arrayexpress
Project description:MCF-7 serum withdrawal (Agilent mouse 60K microarray)
| PRJNA1163901 | ENA
Project description:This study demonstrates that TS5-p45 induces endothelial cell (EC) apoptosis in a caspase-dependent manner via its cell surface receptor Nucleolin (NCL). To unravel how this apoptosis mechanism is induced in ECs, we performed RNA-seq using TS5-p45-treated ECs. Transcriptional changes under TS5-p45 treatment was further evaluated to highlight some of the caspase-dependent apoptosis-inducing and -suppressing genes which are altered in favor of apoptosis.
2022-03-02 | GSE191049 | GEO
Project description:Kindling induced by Pentylenetetrazol is an established rodent model of epileptogenesis. The molecular basis of the long-term plasticity involved is however not clear. In addition, rodent models of kindling plasticity are not useful for large-scale screening of compounds to identify antiepileptogenic drugs. Given this, we have developed a fly model of chronic PTZ- and withdrawal-induced behavioral plasticity. In our fly model, the chronic PTZ treatment is given for 7 days. This is then followed by 7 day long withdrawal. Expression profiling of fly heads at three time points in the 7 day long withdrawal period – 8th day, 10th day, and 14th day from the beginning of the treatment - showed a dynamic and widespread alteration of various functional categories of genes. Keywords: time series
2007-10-02 | GSE7156 | GEO
Project description:The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to an imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depleted key TCA cycle metabolites and, in combination with MYC activation, led to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses revealed that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC- driven lymphoma in vivo. In summary, glutamine supports the viability of MYC- overexpressing cells through an energetic rather than a biosynthetic mechanism.
2022-08-11 | PXD034517 | Pride
Project description:Background: A comprehensive understanding of the determinants of endothelial cell (EC) lineage specification will advance strategies for cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures specifically regulate cell identity genes, making it possible to systematically identify novel EC master regulators by leveraging extensive epigenomic datasets available for EC. Methods: We developed a method to identify novel regulators of endothelial cell identity by integrating multiple epigenetic patterns. We verified MEOCM as a master EC lineage regulator using both in vivo and in vitro experiments. The mechanism of action of MECOM as EC lineage regulator was characterized by integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, scRNA-seq and bulk RNA-Seq data, as well as extensive molecular, cellular, and animal experiments. Results: We identified MECOM to be the leading candidate as an EC lineage regulator. Single-cell RNA-Seq analysis further revealed that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide iPSC-ECs. We verified that MECOM was required for human endothelial differentiation, EC functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate EC identity genes. Specifically, we identified the VEGF signaling pathway to be a key downstream target of MECOM. Conclusions: Our work provides new insights into epigenetic regulation of cell identity genes and uncovered MECOM as a master regulator of EC identity.
2023-03-16 | GSE160647 | GEO
Project description:Estrogens have been shown to elicit anti-cancer effects against estrogen receptor alpha (ER)-positive breast cancer. We sought to determine the underlying mechanism of therapeutic response. Response to 17b-estradiol was assessed in ER+ breast cancer models with resistance to estrogen deprivation: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells. As another means to reactivate ER, the anti-estrogen fulvestrant was withdrawn from fulvestrant-resistant MCF-7 cells. Transcriptional, growth, apoptosis, and molecular alterations in response to ER reactivation were measured. 17b-estradiol treatment and fulvestrant withdrawal induced transcriptional activation of ER, and cells adapted to estrogen deprivation or fulvestrant were hypersensitive to 17b-estradiol. ER transcriptional response was followed by an unfolded protein response and apoptosis. Such apoptosis was dependent upon the unfolded protein response, p53, and JNK signaling. Anti-cancer effects were most evident in models exhibiting genomic amplification of the gene encoding ER (ESR1), suggesting that engagement of ER at high levels is cytotoxic. These data indicate that long-term adaptation to estrogen deprivation or ER inhibition alters sensitivity to ER reactivation. In such adapted cells, 17b-estradiol treatment and anti-estrogen withdrawal hyperactivate ER, which drives an unfolded protein response activation and subsequent growth inhibition and apoptosis. 17b-estradiol treatment should be considered as an alternative therapy for anti-estrogen-resistant disease, particularly in patients with tumors harboring ESR1 amplification or overexpression. Furthermore, therapeutic strategies that enhance an unfolded protein response may enhance the therapeutic effects of ER reactivation.
2019-08-19 | GSE121379 | GEO
Project description:Doxorubicin (DOX), an effective chemotherapeutic drug for various cancers, has been demonstrated to induce cardiovascular toxicity in cancer survivors. Endothelial cell (EC) dysfunction is recognized to play a critical role in the onset and severity of cardiotoxicity associated with DOX. Transcription factor EB (TFEB), a master autophagy regulator, regulates cardiovascular homeostasis. In the present study, we aimed to test whether endothelial TFEB protects against EC damage after DOX treatment.
2025-12-18 | GSE237200 | GEO
Project description:Sepsis is an exaggerated immune response upon infection with lipopolysaccharide (LPS) as the main causative agent. LPS-induced activation and apoptosis of endothelial cells (EC) can lead to organ dysfunction and finally organ failure. We have previously demonstrated that the first twenty amino acids of the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) are sufficient to inhibit EC apoptosis. To identify genes whose regulation by LPS is affected by this N-terminal APEX1 peptide, EC were transduced with an expression vector for the APEX1 peptide or an empty control vector and treated with LPS. Following RNA deep sequencing, genes upregulated in LPS-treated EC expressing the APEX1 peptide were identified bioinformatically.
2021-09-20 | E-MTAB-10936 | biostudies-arrayexpress
Project description:Background: Endometrial carcinoma (EC) is a common gynecological malignancy with increasing incidence and death rate during the past years. In order to obtain better prognosis, it is necessary to develop novel therapy strategies for EC, especially for molecular targeted therapy. CDC20 is an Anaphase promoting complex/cyclosome (APC/C) activator and has been reported to exhibit an oncogenic function. Thus, CDC20 could be a promising therapeutic target for EC. Methods: The expression of CDC20 was analyzed based on TCGA databases and Human Protein Atlas and verified in EC cell lines by western blotting. We evaluated the anti-tumor effects of CDC20 inhibitor Apcin on proliferation, apoptosis, cell cycle and mobility of EC cell lines, AN3CA and KLE, by CCK8 assay, flow cytometer analysis, wound healing and transwell assay respectively. Furthermore, we performed RNA-sequencing on EC cells with or without Apcin treatment and conducted bioinformatics analysis to explore the molecular mechanism. The differentially expressed genes were verified by PCR and western blotting. Results: TCGA data reveal that the expression level of CDC20 is higher in EC tissue than in nonmalignant tissue. Stable and high expression of CDC20 was also detected in EC cell lines. Treatment with CDC20 inhibitor Apcin inhibited proliferation and induced apoptosis while did not influence mobility ability of EC cells. The effects of Apcin treatment on cell cycle distribution were different between these two EC cell lines. The percentage of G2/M phase cells was increased in Apcin-treated KLE cells but did not change significantly in Apcin-treated AN3CA cells. Bioinformatics analysis of RNA-seq data identified that apoptosis, P53 pathway and TNF signaling pathway were activated in EC cells after Apcin treatment, indicating the potential mechanisms through which Apcin exerted its antitumor function. Furthermore, the anti-tumor effects of Apcin are related to the regulation of BBC3 and P21 expression in EC cells. Conclusions: CDC20 is a promising molecular target and Apcin may be a potential pharmaceutics for EC treatment. CDC20 is a novel molecular target in EC, which highlights Apcin as a candidate drug in targeted therapy of EC.
2024-06-30 | GSE167548 | GEO