Phosphoenol-pyruvate carboxykinase isoform 2 (PCK2) causes metabolic defects in endothelial cells and angiogenesis.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Homo sapiens
SUBMITTER: Shawez Khan
PROVIDER: E-MTAB-8104 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Given the prominent angiogenic impairment in PHGDHECKO mice and the proliferation defect of PHGDHKD ECs, which could not fully be explained by a decreased one carbon metabolism pool, together with the observed impairment of mitochondrial homeostasis and reduced respiration in PHGDHKD ECs, we performed an RNA-seq analysis of control and PHGDHKD ECs.
2018-08-29 | E-MTAB-5368 | biostudies-arrayexpress
Project description:Endothelial cell (EC) metabolism regulates angiogenesis and is an emerging target for anti-angiogenic therapy in tumor and choroidal neovascularization (CNV). In contrast to tumor ECs (TECs), CNV-ECs cannot be isolated for unbiased metabolic target discovery. Here we used scRNA-sequencing to profile 28,337 choroidal ECs (CECs) from mice to in silico distinguish healthy CECs from CNV-ECs. Trajectory inference suggested that CNV-ECs plastically upregulate genes in central carbon metabolism and collagen biosynthesis during differentiation from quiescent postcapillary venous ECs. CEC-tailored genome scale metabolic modeling predicted essentiality of SQLE and ALDH18A1 for proliferation and collagen production, respectively. Comparative analysis in TECs revealed more outspoken metabolic transcriptome heterogeneity in subtypes and consistent upregulation of SQLE and ALDH18A1 across tumor types. Inhibition of SQLE and ALDH18A1 reduced sprouting angiogenesis in vitro. These findings demonstrate the potential of integrated scRNA-seq analysis to identify angiogenic metabolic targets in disease ECs.
2020-06-25 | E-MTAB-8119 | biostudies-arrayexpress
Project description:Phosphoenol-pyruvate carboxykinase isoform 2 (PCK2) causes metabolic defects in endothelial cells and angiogenesis.
| PRJEB33275 | ENA
Project description:Endothelial cell (EC) metabolism is an emerging target for anti-angiogenic therapy in tumor and choroidal neovascularization (CNV), but little is known about individual EC metabolic transcrip-tomes. Here, by scRNA-sequencing 28,337 murine choroidal ECs (CECs) and sprouting CNV-ECs, we constructed a taxonomy to characterize their heterogeneity. Comparison with murine lung tumor ECs (TECs) revealed congruent marker gene expression by distinct EC phenotypes across tissues and diseases, suggesting similar angiogenic mechanisms. Trajectory inference of CNV-ECs revealed that differentiation of venous to angiogenic ECs was accompanied by metabolic transcriptome plasticity. EC phenotypes displayed metabolic transcriptome heterogeneity. Hypothesizing that conserved genes are more important, we used an integrated analysis, based on congruent transcriptome analysis, CEC-tailored genome scale metabolic modeling, and gene expression me-ta-analysis in multiple cross-species datasets, followed by functional validation, to identify the top-ranking metabolic targets SQLE and ALDH18A1, involved in EC proliferation and collagen production, respectively, as novel angiogenic targets.
2020-03-31 | E-MTAB-8604 | biostudies-arrayexpress
Project description:The heterogeneity of endothelial cells (ECs), lining blood vessels, across tissues remains incompletely inventoried. We constructed an atlas of >32,000 single-EC transcriptomic data from 11 tissues of the model organism Mus musculus. We propose a new classification of EC phenotypes based on transcriptome signatures and inferred putative biological features. We identified top-ranking markers for ECs from each tissue. ECs from different vascular beds (arteries, capillaries, veins, lymphatics) resembled each other across tissues, but only arterial, venous and lymphatic (not capillary) ECs shared markers, illustrating a greater heterogeneity of capillary ECs. We identified high-endothelial-venule and lacteal-like ECs in the intestines, and angiogenic ECs in healthy tissues. Metabolic transcriptomes of ECs differed amongst spleen, lung, liver, brain and testis, while being similar for kidney, heart, muscle and intestines. Within tissues, metabolic gene expression was heterogeneous amongst ECs from different vascular beds, altogether highlighting large EC heterogeneity.
2020-02-13 | E-MTAB-8077 | biostudies-arrayexpress
Project description:The endothelium is the frontline target of multiple metabolic stressors and pharmacological agents. As a consequence, endothelial cells (ECs) display highly dynamic and diverse proteome profiles. We describe here the culture of human aortic ECs from healthy and type 2 diabetic donors, the treatment with a small molecular conformation of trans-resveratrol and hesperetin (tRES+HESP), followed by proteomic analysis of whole-cell lysate. A number of 3666 proteins were presented in all the samples and thus further analyzed. We found that 179 proteins had a significant difference between diabetic ECs vs. healthy ECs, while 81 proteins had a significant change upon the treatment of tRES+HESP in diabetic ECs. Among them, 16 proteins showed a difference between diabetic ECs and healthy ECs and the difference was reversed by the tRES+HESP treatment, with the top 5 drastically altered proteins being ACVRL1, ADAM9, ITGAV, PCCB, and TGFBR2. Follow-up functional assays identified ACVRL1 and TGFBR2 as the most pronounced mediator for tRES+HESP-induced protection of angiogenesis in vitro. Our study has revealed the global changes in proteins and biological pathways in ECs from diabetic donors, which are potentially reversible by the tRES+HESP formula. Furthermore, we have identified the TGFβ signaling axis as a responding mechanism in ECs treated with this formula, shedding light for future studies for deeper molecular characterization
2023-07-20 | PXD036094 | Pride
Project description:Little is known about the function of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) generated from diabetics, as this could potentially limit subsequent therapeutic use in this patient population. Here, we demonstrate that iPSC-ECs derived from diet-induced obesity (DIO) mice exhibit evidence of endothelial dysfunction. We also observed that mice receiving intramuscular (IM) injections of DIO iPSC-ECs had significantly decreased reperfusion following hindlimb ischemia compared to mice administered with iPSC-ECs from control mice. Hindlimb sections revealed increased muscle atrophy and presence of inflammatory cells in mice receiving iPSC-ECs from DIO mice. When pravastatin was administered to mice receiving DIO iPSC-ECs, a significant increase in reperfusion was observed, which was blunted by co-administration of L-NAME. This study is the first to provide evidence that iPSC-ECs from pre-diabetic mice exhibit signs of endothelial function, and suggest that pravastatin administration may be needed for diabetic patients receiving autologous iPSC-ECs therapy in the clinic. Four samples were analyzed, two from the healthy (control) group and two from the diet-induced obesity group
2014-01-25 | E-GEOD-54387 | biostudies-arrayexpress
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes involved in plaque rupture. Human coronary artery endothelial cells (ECs) were stimulated in vitro for 12 hours with plasma obtained from the coronary sinus (CS) and the aorta (Ao) of patients with ACS (n=8), or patients with stable angina (SA, n=4). For each patient, gene expression profile was evaluated by microarray technology in ECs exposed to plasma obtained from CS and compared to that of ECs exposed to plasma sampled from Ao. In patient with ACS we found 684 genes up-regulated and 283 down-regulated was observed as compared to patients with SA. Functional and network analyses of statistically significant gene showed that the up regulated genes were associated to pathways IL17 Signaling. To validate the microarray data the RNAs were used for Real Time PCR experiment. Human coronary artery endothelial cells (ECs) were stimulated in vitro for 12 hours with plasma obtained from the coronary sinus (CS) and the aorta (Ao) of patients with ACS (n=8), or patients with stable angina (SA, n=4). For each patient, gene expression profile was evaluated by microarray technology in ECs exposed to plasma obtained from CS and compared to that of ECs exposed to plasma sampled from Ao.
2014-02-14 | E-GEOD-54977 | biostudies-arrayexpress
Project description:Snail1 is a master factor of epithelial to mesenchymal transitioin (EMT), however, its role in embryonic vascular development is largely undefined. We used microarrays to compare the global programme of gene expression between cultured WT and Snai1 KO embyronic ECs. ECs isolated from E10.5 Snail1f/f embryos were infected with adeno-?Gal or -Cre to generate WT and Snail1 KO ECs. RNA were collected for Affymetrix microarrays.
2014-04-24 | E-GEOD-57030 | biostudies-arrayexpress
Project description:The ventromedial nucleus of the hypothalamus (VMH) is thought to a satiety center and a potential target for anti-obesity therapy. Electroconvulsive seizure (ECS) therapy is highly effective in psychiatric diseases including depression, but also implicated beneficial effects on other neurological diseases. Although it has been reported that the neurons in the VMH are strongly activated by ECS stimulation, the effect of ECS in this hypothalamic subnucleus remains unknown. To address this issue, we investigated molecular changes in the VMH in response to ECS by utilizing a method of laser-capture microdissection coupled with microarray analysis, and examined behavioral effects of ECS via VMH activation. ECS significantly induced gene expression not only immediate-early genes such as Fos, Fosb and Jun, but also Bdnf, Adcyap1, and Hrh1 in the VMH after a single or repeated stimulus. Mice received one or 7 times shock of ECS and their brains were collected at 2 h (VMH_1stECS2h, VMH_7thECS2h) or 6 h after shock (VMH_1stECS6h, VMH_7thECS6h). The brains of sham-treated animals were collected at 2 h after treatment(VMH_sham). The VMH was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.
2012-05-29 | E-GEOD-38311 | biostudies-arrayexpress