Ontology highlight
ABSTRACT:
PROVIDER: PRJNA943253 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23802800.fastq.gz | Fastqsanger.gz | |||
| SRR23802802_1.fastq.gz | Fastqsanger.gz | |||
| SRR23802802_2.fastq.gz | Fastqsanger.gz | |||
| SRR23802803_1.fastq.gz | Fastqsanger.gz | |||
| SRR23802803_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Systematic elucidation of genetic mechanisms underlying cholesterol uptake
| PRJNA955219 | ENA
Project description:Systematic elucidation of genetic mechanisms underlying cholesterol uptake
2023-04-21 | GSE229650 | GEO
Project description:Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be defined. We therefore quantified cholesterol and phospholipid concentrations in intestine and liver and determined fecal neutral sterol and bile acid excretion in C57Bl/6N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat diet containing 0.03 % (w/w) cholesterol. To identify underlying mechanisms of dietary adaptation in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Animals on high fat diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load. The proximal part of the intestine of mice fed either a control or a high fat diet were analyzed. 5 replicates each.
2011-08-31 | E-GEOD-29748 | biostudies-arrayexpress
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146108 | GEO
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146107 | GEO
Project description:Microglia are emerging as key drivers of neurological diseases. However, we lack a systematic understanding of the underlying mechanisms. Here, we present a screening platform that enables the systematic elucidation of functional consequences of genetic alterations in human iPSC-derived microglia. We developed a protocol based on the inducible expression of six transcription factors, which generates microglia-like cells in an efficient eight-day protocol which was confirmed by bulk RNA sequencing. We established inducible CRISPR interference and activation in this system and conducted three screens targeting the “druggable genome” that uncovered genes controlling microglia survival, activation and phagocytosis, including neurodegeneration-associated genes. A screen with single-cell RNA sequencing readout revealed that these microglia adopt a spectrum of states mirroring those observed in human brains and identifies regulators of these states. A disease-associated state characterized by SPP1 expression is selectively depleted by CSF1R inhibition.Thus, our platform can systematically uncover regulators of microglia states, enabling their functional characterization and therapeutic targeting.
2021-06-17 | GSE178317 | GEO
Project description:Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be defined. We therefore quantified cholesterol and phospholipid concentrations in intestine and liver and determined fecal neutral sterol and bile acid excretion in C57Bl/6N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat diet containing 0.03 % (w/w) cholesterol. To identify underlying mechanisms of dietary adaptation in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Animals on high fat diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.
2011-09-01 | GSE29748 | GEO
Project description:Intricate regulatory networks govern the net balance of cholesterol biosynthesis, uptake and efflux; however, the mechanisms surrounding cholesterol homeostasis remain incompletely understood. Here, we develop an integrative genomic strategy to detect regulators of LDLR activity and identify 250 genes whose knockdown affects LDL-cholesterol uptake and whose expression is modulated by intracellular cholesterol levels in human hepatic cells. From these hits, we focus on MMAB, an enzyme which catalyzes the conversion of vitamin B12 to adenosylcobalamin, and whose expression has previously been linked with altered levels of circulating cholesterol in humans. We demonstrate that hepatic levels of MMAB are modulated by dietary and cellular cholesterol levels through SREBP2, the master transcriptional regulator of cholesterol homeostasis. Knockdown of MMAB decreases intracellular cholesterol levels and augments SREBP2-mediated gene expression and LDL-cholesterol uptake in human and mouse hepatic cell lines. Reductions in total sterol content were attributed to increased intracellular levels of propionic and methylmalonic acid and subsequent inhibition of HMGCR activity and cholesterol biosynthesis. Moreover, mice treated with antisense inhibitors of MMAB display a significant reduction in hepatic HMGCR activity, hepatic sterol content and increased expression of SREBP2-mediated genes. Collectively, these findings reveal an unexpected role for the adenosylcobalamin pathway in regulating LDLR expression and identify MMAB as an additional control point by which cholesterol biosynthesis is regulated by its end product.
2021-09-10 | GSE183790 | GEO
Project description:Intricate regulatory networks govern the net balance of cholesterol biosynthesis, uptake and efflux; however, the mechanisms surrounding cholesterol homeostasis remain incompletely understood. Here, we develop an integrative genomic strategy to detect regulators of LDLR activity and identify 250 genes whose knockdown affects LDL-cholesterol uptake and whose expression is modulated by intracellular cholesterol levels in human hepatic cells. From these hits, we focus on MMAB, an enzyme which catalyzes the conversion of vitamin B12 to adenosylcobalamin, and whose expression has previously been linked to altered levels of circulating cholesterol in humans. We demonstrate that hepatic levels of MMAB are modulated by dietary and cellular cholesterol levels through SREBP2, the master transcriptional regulator of cholesterol homeostasis. Knockdown of MMAB decreases intracellular cholesterol levels and augments SREBP2-mediated gene expression and LDL-cholesterol uptake in human and mouse hepatic cell lines. Reductions in total sterol content were attributed to increased intracellular levels of propionic and methylmalonic acid and subsequent inhibition of HMGCR activity and cholesterol biosynthesis. Moreover, mice treated with antisense inhibitors of MMAB display a significant reduction in hepatic HMGCR activity and hepatic sterol content and increased expression of SREBP2-mediated genes. Collectively, these findings reveal an unexpected role for the adenosylcobalamin pathway in regulating LDLR expression and identify MMAB as an additional control point by which cholesterol biosynthesis is regulated by its end product.
2021-06-01 | GSE169712 | GEO
Project description:Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated multi-omics datasets for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. This experiment contains data from RNA-sequencing of human post-mortem brain tissue of the frontal lobe from patients with FTD caused by mutations in GRN, MAPT or C9orf72 and healthy controls.
2023-02-17 | E-MTAB-12647 | biostudies-arrayexpress