Single cell analysis of epithelial (EPI), immune (IMM) and stromal cells (double negative, DN) cells from murine small intestine in steady state following LXR activation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227726 | GEO | 2024/07/19
REPOSITORIES: GEO
Similar Datasets
Project description:Liver X receptors (LXRα and LXRβ) are nuclear receptor transcription factors that play crucial roles in regulating metabolic and immune functions in macrophages. Both receptors are present in macrophages and exhibit significant sequence similarity, yet their specific roles in various macrophage models, especially in inflammatory contexts, remain underexplored. Prior research has demonstrated that ligand-activated LXRs can suppress the expression of pro-inflammatory cytokines in macrophages. Here, we explored the genomic landscape of LXRa under inflammatory conditions using BMDM lacking LXRb as previously described (de la Rosa et al 2024); we treated BMDM with synthetic LXR ligand GW3965 alone or in combination with lipopolysaccharide for 24h.
2024-08-27 | GSE275506 | GEO
Project description:Liver X receptors (LXRs) are important regulators of cholesterol, lipid and glucose metabolism and have been extensively studied in liver, macrophages and adipose tissue. However, their role in skeletal muscle is not yet fully elucidated and the functional role of each of the LXRM-NM-1 and LXRM-NM-2 subtypes in skeletal muscle is at present unknown. To study the importance of each of the receptor subtypes, myotube cultures derived from wild type (WT), LXRM-NM-1 and LXRM-NM-2 knockout (KO) mice were established. The present study shows that treatment with the unselective LXR agonist T0901317 increased mRNA levels of LXR target genes such as sterol regulatory element-binding transcription factor 1 (SREBF1), fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1) and ATP-binding cassette transporter A1 (ABCA1) in myotubes established from WT and LXRM-NM-1 KO mice. However, only minor changes in expression level were observed for these genes after treatment with T0901317 in myotubes from LXRM-NM-2 KO mice. Gene expression analysis using Affymetrix NuGO Genechip arrays showed that few other genes than the classical, well known LXR target genes were regulated by LXR in skeletal muscle. Furthermore, functional studies using radiolabeled substrates showed that treatment with T0901317 increased lipogenesis and apoA1 dependent cholesterol efflux, in myotubes from WT and LXRM-NM-1 KO mice, but not LXRM-NM-2 KO mice. The data suggest that the lipogenic effects of LXRs, as well as the LXR-stimulated cholesterol efflux, are mainly mediated by LXRM-NM-2 in skeletal muscle. To study the importance of each of the receptor subtypes, myotube cultures derived from wild type (WT), LXRa and LXRb knockout (KO) mice were established. Sixteen samples were examined. Half the samples were treated with the unselective LXR agonist T0901317.
2010-03-30 | E-GEOD-13192 | biostudies-arrayexpress
Project description:The objective of the study was to figure out the impact of LXR signaling on human macrophages. Primary human macrophages in an early differentiating and a mature differentiation state were treated with the LXR agonist T091317 for 4 and 24 h and transcriptome-wide expression analysis were performed. As LXRa is highly induced during macrophage differentiation and 68% of all LXRs targets change their expression during this process, we suggest that LXRs have essential functions in macrophage development. More than 238 genes are regulated in early as well as mature macrophages by activation of LXRs; most of them are up-regulated. LXRs administrate differentiation state specific as well as common macrophages functions related primarily to lipid homeostasis, immune response and cell fate. Interestingly, almost only genes related to lipid and cholesterol metabolism are overrepresented among early induced genes, whereas genes related to immune functions respond later, implying the existence of indirect mechanisms of control. Furthermore, in early differentiating macrophages cell proliferation and cell death associated genes are induced after 24 h of LXR activation, whereas in mature macrophages, showing high LXRa expression, the same functional cluster respond far earlier (4 h) after LXR ligand treatment. In conclusion, our data suggest that LXRs are modulators of macrophage differentiation, operating principally as positive transcriptional regulators of genes involved in lipid and cholesterol metabolism and by this indirectly influencing the immunophenotype of macrophages. CD14 positive cells of healthy donors were isolated by magnetic separation and differentiated in the presence of human serum to macrophages. At an early differentiating state (16 h after isolation) and at in mature differentiating state (day 11 after isolation) the cells were treated with the synthetical LXR agonist T091317 respective its solvent DMSO for 4 and 24 h. RNA was isolated and a whole genome microarray was performed.
2014-12-19 | E-GEOD-35967 | biostudies-arrayexpress
Project description:The objective of the study was to figure out the impact of LXR signaling on human macrophages. Primary human macrophages in an early differentiating and a mature differentiation state were treated with the LXR agonist T091317 for 4 and 24 h and transcriptome-wide expression analysis were performed. As LXRa is highly induced during macrophage differentiation and 68% of all LXRs targets change their expression during this process, we suggest that LXRs have essential functions in macrophage development. More than 238 genes are regulated in early as well as mature macrophages by activation of LXRs; most of them are up-regulated. LXRs administrate differentiation state specific as well as common macrophages functions related primarily to lipid homeostasis, immune response and cell fate. Interestingly, almost only genes related to lipid and cholesterol metabolism are overrepresented among early induced genes, whereas genes related to immune functions respond later, implying the existence of indirect mechanisms of control. Furthermore, in early differentiating macrophages cell proliferation and cell death associated genes are induced after 24 h of LXR activation, whereas in mature macrophages, showing high LXRa expression, the same functional cluster respond far earlier (4 h) after LXR ligand treatment. In conclusion, our data suggest that LXRs are modulators of macrophage differentiation, operating principally as positive transcriptional regulators of genes involved in lipid and cholesterol metabolism and by this indirectly influencing the immunophenotype of macrophages.
2014-12-19 | GSE35967 | GEO
Project description:The nuclear receptors LXRa and LXRb play a crucial role in regulating hepatic lipid metabolism. Many genes induced in response to pharmacologic LXR agonism in mouse liver have been defined; however, the transcriptional consequences of loss of LXR binding to its genomic targets are not well characterized. Here we addressed how deletion of both LXRa and LXRb from mouse liver (LXRDKO) affects the transcriptional regulatory landscape by integrating changes in LXR/RXR binding, chromatin accessibility, and gene expression. Many genes involved in fatty acid metabolism have reduced expression and chromatin accessibility at their intergenic and intronic regions in LXRDKO livers. Genes that were upregulated in LXRDKO livers have increased chromatin accessibility in their promoter regions and are enriched for those with functions not linked to lipid metabolism. We further showed that loss of LXR binding in liver reduces the activity of a broad set of hepatic transcription factors, inferred through motif accessibility. In contrast, accessibility at promoter NFY motifs is strongly increased in the absence of LXR. Surprisingly, we define small set of direct target genes for ligand-dependent LXR repression. These genes with LXR binding sites show increased expression in LXRDKO liver and reduced expression in response to LXR agonist treatment. In summary, while our results support the established roles for LXRs as ligand-dependent activators of genes linked to lipid metabolism, the binding of LXR/RXR heterodimers to the hepatic genome has broad effects on the transcriptional landscape that extend beyond its canonical function as an activator of lipid metabolic genes.
2022-01-25 | GSE191030 | GEO
Project description:In this dataset, we investigate the murine small intestine spatial transcriptomic profile at the steady state and compare the genes alteration with and without LXR activation by sythetic ligand GW3965 diet.
2024-07-19 | GSE267029 | GEO
Project description:The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways, including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand the knowledge of the functions of LXR signaling during embryonic development, we performed a whole-genome microarray analysis of Lxr target genes in zebrafish larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965. Assessment of the biological processes enriched by differentially expressed genes revealed a prime role for Lxr in regulating lipid metabolic processes, similarly to the function of LXR in mammals. In addition, exposure to the Lxr ligands induced changes in expression of genes in the neural retina and lens of the zebrafish eye, including the photoreceptor guanylate cyclase activators and lens gamma crystallins, suggesting a potential novel role for Lxr in modulating the transcription of genes associated with visual function in zebrafish. The regulation of expression of metabolic genes was phenotypically reflected in an increased absorption of yolk in the zebrafish larvae, and changes in the expression of genes involved in visual perception were associated with morphological alterations in the retina and lens of the developing zebrafish eye. The regulation of expression of both lipid metabolic and eye specific genes was sustained in 1 month old fish. The transcriptional networks demonstrated several conserved effects of LXR activation between zebrafish and mammals, and also identified potential novel functions of Lxr, supporting zebrafish as a promising model for investigating the role of Lxr during development.
2016-03-07 | GSE59031 | GEO
Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes AML-12 cells co-treated with 0.75mM PA+/- 10µM GW3965 for 24 h +/- Ulk1 SiRNA
2016-03-31 | E-GEOD-74059 | biostudies-arrayexpress
Project description:Melanoma metastasis is a devastating outcome in need of novel preventive therapies. We provide pharmacologic, nolecuar, and genetic evidence establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target in melanoma. Molecular and genetic experiments revealed these effects to be mediated by LXRb, which elicits these outcomes through transcriptional induction of tumoral and systemic apolipoprotein-E (ApoE). LXRb agonism robustly suppressed tumor growth and metastasis across a wide spectrum of melanoma lines of diverse mutational subtypes established in xenograft, immunocompetent, and genetically-initiated model. We propose a path for the clinical testing of LXRb targeting-a therapeutic approach that uniquely acts by transcriptionally acivating a metastasis suppressor gene. In this experiment we analyzed the effect of GW3965 treatment on gene expression in the MeWo human melanoma cell line. The cells were treated either with DMSO or GW3965 at 1 micromolar for 48 hours, after which the RNA was extracted and gene expression was analyzed by transcriptomic profiling
2014-06-01 | E-GEOD-48782 | biostudies-arrayexpress
Project description:Endothelial progenitor cells (EPCs) promote the maintenance of the endothelium by secreting vasoreparative factors. A population of EPCs known as early outgrowth cells (EOCs) are being investigated as novel cell-based therapies for the treatment of cardiovascular disease. We previously demonstrated that the absence of liver x receptors (LXRs) is detrimental to the formation and function of EOCs under hypercholesterolemic conditions. Here, we investigate whether LXR activation in EOCs is beneficial for the treatment of atherosclerosis. EOCs were differentiated from the bone marrow of wildtype (WT) and LXR-knockout (Lxrαβ-/-) mice in the presence of vehicle or LXR agonist (GW3965). This data set is a proteomic comparison of EPCs at day 1 after isolation and day 9 of GW39565 treatment compared to day 9 of vehicle treatment.
2021-09-09 | PXD021993 | Pride