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
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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: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: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:Gene expression profiling of endothelial cell apoptosis induced by serum withdrawal
| PRJNA129877 | ENA
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:Human beings are unable to synthetize the glycolylated neuraminidic acid (Neu5Gc) following a mutation of the CMAH gene and diet induced anti-Neu5Gc antibodies develop in the first year of life. However, because humans can absorb Neu5Gc which deposits at low levels on endothelial cells (EC), activation of endothelium by anti-Neu5Gc has been raised. Understanding whether this interaction contributes to EC normal biology or may induce a potentially detrimental EC activation is crucial, particularly in patients developing elicited anti-Neu5Gc following introduction of animal derived molecules or bio-devices. Ten EC lines were cultured with immune-affinity purified anti-Neu5Gc from normal sera (diet induced) or sera harvested following rabbit-IgG infusion (elicited) anti-Neu5Gc. After a 4h-incubation of Neu5Gc loaded ECs at levels close to those of freshly harvested ECs, ECs were stimulated with both anti-Neu5Gc types and with or without human complement. Anti-Neu5Gc induce a differential expression (DE) of 967 out of expressed 12,208 genes, with transcript accumulation in 93%. Most DE transcripts are shared following activation by pre-existing or elicited anti-Neu5Gc. Compared to ATG pre-existing antibodies, elicited anti-Neu5Gc down-regulated 66 genes, involving master genes such as IL8, ICAM1, MAPKINASES or NFKb1. Furthermore, addition of elicited anti-Neu5Gc to non-heat inactivated sera down-regulated most of the transcripts mobilized by serum alone, including key transcripts involved in apoptosis, fitting with no increase in apoptotic cells. Altogether, the RNA profiling following culture of human ECs and anti-Neu5Gc suggests that pre-existing anti-Neu5Gc contribute to normal human EC homeostasis rather than to an inflammatory oriented transcriptome. Elicited anti-Neu5Gc do not also skew EC transcriptome toward inflammation either, but trigger the release cytokines or chemokines in culture supernatants.
2019-07-18 | GSE117146 | GEO
Project description:Old Human Serum Increases Apoptosis and Molecular Ageing Markers In Human Hippocampal Progenitor Cells
| PRJNA416774 | ENA
Project description:Serum TNF-α plays a key role in mediating inflammation and apoptosis in renal tubular cells and indicates PCOS-related kidney injury.
2023-12-06 | GSE229106 | 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:Objective M-bM-^@M-^S Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased approach. Approach and Results M-bM-^@M-^S In human umbilical vein endothelial cells, microarray analysis of gene expression followed by pathway enrichment analysis and qRT-PCR validation revealed that telmisartan modulates the expression of key genes responsible for cell cycle progression and apoptosis. AmlodipineM-bM-^@M-^Ys effect was similar to control. EC exposed to telmisartan, but not amlodipine, losartan or valsartan, exhibited a dose-dependent impairment of cell growth and failed to enter the S-phase of the cell cycle. Similarly, telmisartan inhibited proliferation in COS-7 cells lacking the AT1 receptor. In telmisartan-treated EC, phosphorylation and activation of Akt as well as MDM2 was reduced, leading to accumulation of p53 in the nucleus, where it represses the transcription of cell cycle promoting genes. Phosphorylation of GSK3M-NM-2 was also reduced, resulting in rapid proteolytic turnover of CyclinD1. Telmisartan induced downregulation of proapoptotic genes and protected EC from serum starvation- and 7-ketocholesterol-induced apoptosis. Conclusions M-bM-^@M-^S Telmisartan exerts antiproliferative and antiapoptotic effects in EC. This may account for the improved endothelial dysfunction observed in the clinical setting. HUVEC were treated with 100 M-BM-5mol/L telmisartan or 5 M-BM-5mol/L amlodipine or both in dimethyl sulfoxide (DMSO) or an equivalent volume of DMSO alone, as control, for 24 hours. Microarray analysis was carried out on two biological replicates per group (total of six samples). See PROTOCOL section for experimental details.
2013-05-14 | E-GEOD-42808 | biostudies-arrayexpress