Ontology highlight
ABSTRACT:
PROVIDER: PRJNA702242 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13727575_1.fastq.gz | Fastqsanger.gz | |||
| SRR13727575_2.fastq.gz | Fastqsanger.gz | |||
| SRR13727576_1.fastq.gz | Fastqsanger.gz | |||
| SRR13727576_2.fastq.gz | Fastqsanger.gz | |||
| SRR13727577_1.fastq.gz | Fastqsanger.gz |
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Project description:Single-cell Atlas Reveals Fatty Acid Metabolites Regulate the Functional Heterogeneity of Mesenchymal Stem Cells
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Project description:Mesenchymal stem cells (MSCs) are present in the circulation of cancer patients, and are recruited to the stroma of both the primary tumor and metastasis. Recent preclinical research has shown that in response to platinum-based chemotherapy, MSCs secrete two specific platinum-induced fatty acids (PIFAs) which induce resistance to a broad spectrum of chemotherapies. The secreted PIFAs are the fatty acid oxo-heptadecatetraenoic acid (KHT) and the omega-3 fatty acid hexadecatetraenoic acid (16:4). These PIFAs are produced via the COX-1 pathway. COX inhibitors, including indomethacin. This phase 1 study explores the safety of combining indomethacin with platinum containing chemotherapy.
| 2134582 | ecrin-mdr-crc
Project description:The aim of this study was to explore the gene expression and metabolites among multisite adipose-derived mesenchymal stem cells, and investigate the metabolic pathway of multisite adipose-derived mesenchymal stem cells using a multi-omics analysis. Subcutaneous adipose-derived mesenchymal stem cells (SASCs), perirenal adipose-derived mesenchymal stem cells (PASCs), and epididymal adipose-derived mesenchymal stem cells (EASCs) were isolated from Sprague Dawley rats. RNA and metabolites were extracted and sequenced using transcriptomics and metabolomics analyses, respectively. There were 720 differentially expressed genes (DEGs) in EASCs and 688 DEGs in PASCs compared with SASCs; there were 166 unique DEGs in EASCs, 134 unique DEGs in PASCs, and 554 common DEGs between EASCs and PASCs. Furthermore, there were 220 differential metabolites in EASCs, 249 differential metabolites in PASCs, 83 unique differential metabolites in EASCs, 112 unique differential metabolites in PASCs, and 137 common differential metabolites between EASCs and PASCs. The transcriptomics and metabolomics analyses identified four hub genes, one in EASCs and three in PASCs. There are functional differences among multisite adipose-derived mesenchymal stem cells that may be related to the hub genes Atac2, Rrm1, Rrm2, and Gla. The relevant signaling pathways are the Ras signaling pathway, HIF-1 signaling pathway, and the p53 signaling pathway.
2021-03-11 | GSE161312 | GEO
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:Mitochondrial trifunctional protein deficiency, due to mutations in hydratase subunit A (HADHA), results in sudden infant death syndrome with no cure. To reveal the disease etiology, we generated stem cell-derived cardiomyocytes from HADHA-deficient hiPSCs and accelerated their maturation via an engineered microRNA maturation cocktail that upregulated the epigenetic regulator, HOPX. Here we report, matured HADHA mutant cardiomyocytes treated with an endogenous mixture of fatty acids manifest the disease phenotype: defective calcium dynamics and repolarization kinetics which results in a pro-arrhythmic state. Single cell RNA-seq reveals a cardiomyocyte developmental intermediate, based on metabolic gene expression. This intermediate gives rise to mature-like cardiomyocytes in control cells but, mutant cells transition to a pathological state with reduced fatty acid beta-oxidation, reduced mitochondrial proton gradient, disrupted cristae structure and defective cardiolipin remodeling. This study reveals that HADHA (tri-functional protein alpha), a monolysocardiolipin acyltransferase-like enzyme, is required for fatty acid beta-oxidation and cardiolipin remodeling, essential for functional mitochondria in human cardiomyocytes.
2019-08-25 | GSE135595 | GEO
Project description:Human neurons engineered from induced pluripotent stem cells (iPSCs) through Neurogenin 2 (Ngn2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here we used single-cell transcriptomics to dissect the cell states that emerge during Ngn2 overexpression across a time course from pluripotency to neuron functional maturation. We find a substantial molecular heterogeneity in the neuron types generated, with at least two populations that express genes associated with neurons of the peripheral nervous system. Neuron heterogeneity is observed across multiple iPSC clones and lines from different individuals. We find that neuron fate acquisition is sensitive to Ngn2 expression level and the duration of Ngn2 forced expression. Our data reveals that Ngn2 dosage can regulate neuron fate acquisition, and that Ngn2-iN heterogeneity can confound results that are sensitive to neuron type.
2021-08-05 | E-MTAB-10632 | biostudies-arrayexpress
Project description:Mesenchymal stem/stromal cells (MSCs) with immunosuppressive properties are increasingly used in advanced cellular therapies. Since the clinical use of hMSCs demands sequential cell expansions, we studied the effect of cell doublings on the phospholipid profile as well as functionality of human bone marrow mesenchymal stem cells (hBMSCs). In addition to the structural role of phospholipids in cell membranes, they provide precursors for eicosanoids and other signalling lipids modulating cellular functions. The hBMSCs, harvested from young adult and old donors (n=5 for both), showed clear compositional changes during cultivation, seen at the level of lipid classes, lipid species and acyl chains. As the main finding at the lipid class level, the ratio of phosphatidylinositol to phosphatidylserine was increased towards the late passage samples. In the species profiles, arachidonic acid (AA) containing species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) clearly accumulated, while the species containing monounsaturated fatty acids decreased. This was related with an increase of AA, a major n-6 polyunsaturated fatty acid (n-6PUFA), in the total fatty acid pool of the cells, which happened at the expense of n-3PUFAs, especially docosahexenoic acid (DHA). Using hBMSCs from four of the young adult donors and four of the old donors, we found that gene expression of several enzymes involved in fatty acid metabolism (such as FADS1, FADS2 and SCD) was altered. The expression of genes related to the regulation of cell cycle, senescence and immunomodulation were altered. Our findings suggest that multistep expansion of hBMSCs alters their fatty acid metabolism and membrane phospholipid composition, which affects lipid signalling and eventually the immune function of the cells. Cultured undifferentiated bone marrow-derived MSCs from old and young donors. Biological replicates: 4 old donors and 4 young donors, passages 4 and 8 from each.
2013-04-05 | E-GEOD-39035 | biostudies-arrayexpress
Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.
2023-07-02 | GSE218319 | GEO
Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.
2023-07-02 | GSE217992 | GEO
Project description:Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triglyceride (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of β-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that β-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells.
2019-01-02 | PXD011854 | Pride