Pnpla2-KO mice snRNAseq
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB72644 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:LSCs have been clinically approved as a cell therapy to treat limbal stem cell deficiency (LSCD), however, there has yet to be a consensus on LSC markers that allow the isolation of LSCs, and their transcriptome profile is not fully understood. In this study, we addressed this problem by using single nuclei RNA sequencing (snRNAseq) on healthy human limbal tissue excised from cataract patients.
2024-08-01 | GSE225355 | GEO
Project description:snRNAseq of human limbus tissue
| PRJNA935339 | ENA
Project description:snRNAseq in human fetal neocortex
| PRJNA885818 | ENA
Project description:Inhibition of adipocyte triglyceride lipase (ATGL/PNPLA2) activity in insulin resistance and non-alcoholic fatty liver disease is an attractive therapeutic target. This study evaluated the impact of Atglistatin-mediated ATGL inhibition on non-alcoholic steatohepatitis (NASH) development in diabetic and hyperlipidaemic mice. Streptozotocin-injected male mice were fed an HFD to induce NASH. We analysed liver histology, hepatic lipid content, immunohistochemistry, RNA sequencing, and serum biochemistry. Mechanistically, we treated Caco2 cells, human primary ileum-derived organoids, and HepG2 ATGL KD cells with the novel human ATGL inhibitor NG-497 and WY14643. Atglistatin reduced body and liver weights, total liver lipid content, and improved blood sugar levels consistent with improved liver enzymes, histological liver injury, and NAFLD activity scores. Mechanistically, Atglistatin reduced Cpt1a and Abca1, suggesting impaired Ppara signalling that favours hydrophilic bile acids (BA) synthesis since Cyp7a1, Cyp27a1, and Cyp2c70 were increased while Cyp8b1 was reduced. Accordingly, Intestinal lipid transporters, Abca1 and Cd36, were reduced, consistent with the reduction of liver TAG species, mostly linoleic acids. We used human-specific ATGL inhibitor NG-497 to validate the mouse findings. The NG-497-treated human primary ileum organoids and Caco2 cells showed reduced ATGL, ABCA1, FATP5, CD36, and MTTP. PPARa signalling was impaired in the ileum organoids and HepG2 treated with NG-497 and in HepG2 ATGL KD since PPARa, CPT1a, AOX, ABCA1, and CYP8B1 were reduced, and CYP7A1 increased. Inhibition of ATGL activity reduces the availability of ligands for Ppara activation leading to impaired Ppara signalling, which translate into hydrophilic BA that interferes with dietary lipid absorption, improving metabolic disturbances. The validation with the NG-497 should open a new clinical avenue for NAFLD clinical trial and treatment.
2024-11-01 | GSE236832 | GEO
Project description:Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. Here, we show that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, leads to neutral lipid accumulation in vessels and impairs endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL leads to endoplasmic reticulum stress-induced inflammation, thereby promoting EC dysfunction. Consistent with this mechanism, deletion of endothelial ATGL markedly increases lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts EC homeostasis and consequently large vessel function during normal physiology and in a chronic disease state
2023-10-31 | GSE246138 | GEO
Project description:Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. Here, we show that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, leads to neutral lipid accumulation in vessels and impairs endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL leads to endoplasmic reticulum stress-induced inflammation, thereby promoting EC dysfunction. Consistent with this mechanism, deletion of endothelial ATGL markedly increases lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts EC homeostasis and consequently large vessel function during normal physiology and in a chronic disease state
2023-12-07 | GSE246083 | GEO
Project description:To investigate the role of ATGL in endothelial cell function, we knockdown ATGL with siRNA and compared with siCTL. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different samples each condition.
2023-11-03 | GSE231619 | GEO
Project description:To investigate the development of aldosterone-producing adenoma, we profiled cells of different areas of the adjacent adrenal cortex by snRNAseq to obtain possible trajectories towards adenoma formation.
2022-08-05 | GSE210381 | GEO
Project description:Abnormalities in neocortical and synaptic development have been associated with neurodevelopmental disorders. However, the molecular and cellular mechanisms regulating the formation of the initial synapses in an evolutionary advanced neocortical layer, the subplate (SP), are poorly understood. Our snRNAseq screen of human prefrontal neocortices from early (11/12 PCW), mid (14/15 PCW) to late (17/18 PCW) fetal developmental stages revealed the bipartite-to-tripartite differentiation of SP neuronal subclasses. Using polysome profiling with RNAseq, we report for the first time a set of mRNAs undergoing translational control in cellular subclasses of developing human prefrontal neocortices, including SP neurons. By examining both mouse and human neocortex, we further found that an autism spectrum disorder (ASD)-risk gene and RNA binding protein CUGBP Elav-Like Family Member 4 (CELF4) is selectively expressed in the neurons of two synapse-enriched compartments, the SP and the marginal zone. Furthermore, CELF4 binds mRNA targets that are encoded by the synaptic genes associated with ASD and adverse neurodevelopmental outcomes; albeit in an evolutionarily advanced fashion between mouse and human synaptic mRNAs. The selective forebrain Celf4 deletion from developing mouse cortical neurons disrupts the balance of SP synapses in a gender-specific fashion. Taken together, our results underscore the importance of RNA binding proteins and mRNA translation in evolutionarily advanced synaptic development, as well as their possible contribution to gender specific protein synthesis and vulnerability.
2023-08-07 | GSE214532 | GEO
Project description:ATGL= the rate-limiting enzyme for intracellular lipolysis. Atgl KO/cTg = Mice lacking Atgl except for cardiac transgenic overexpression of Atgl (Atgl -/- ,Myh6Atgl+/+) to rescue early age death deu to cardiomyopathy. wt/cTg = respective control. The airways of the lung are constantly exposed to inhaled toxic substances, resulting in cellular damage. Within bronchii, club cells make up majority of the cell population in the terminal bronchiolar epithelia. Club cells are known for their ability to metabolize environmental toxins and constantly repairing small impacts in the epithelial layer. Considering the importance of club cells in maintaining bronchiolar epithelial integrity, we porformed gene expression data analysis to decipher the possible dysregulated gene expression thereby corresponding molecular pathways in our mice lacking ATGL.
2021-05-28 | GSE175659 | GEO