Filters
Technology
Platform
GSE48937
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HeLa cells transfected to express KDELR1 and HeLa cells incubated with KDEL-Bodipy peptide
Publication Title
Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
Abstract: The LXR and SREBP transcription factors are key regulators of cellular and systemic cholesterol homeostasis. The molecular mechanisms that integrate these pathways are incompletely understood. Here we show that ligand activation of LXRs in liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as an unexpected mediator of this effect. LeXis is robustly induced in mouse liver in response to western diet feeding or pharmacologic LXR activation. Expression of LeXis in liver inhibits cholesterol biosynthesis and lowers plasma cholesterol levels. Reciprocally, knockdown of LeXis increases hepatic cholesterol content and raises plasma cholesterol levels. LeXis interacts with the heterogeneous nuclear ribonucleoprotein Raly and regulates its binding to cholesterol biosynthetic gene promoters. These studies outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms orchestrating systemic sterol homeostasis. Overall design: Global RNA expression from primary hepatocytes treated with or without GW3965 were compared by RNA-Seq.
Publication Title
Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
GM-CSF receptor- deficient (Csf2rb/ or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rb/mice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rb/ mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rb/ mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile.
Publication Title
Pulmonary macrophage transplantation therapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
ABSTRACT Background: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: Human iPSC-CMs were infected with a luciferase-expressing mutant of the coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs. Viral proliferation on hiPSC-CMs was subsequently quantified using bioluminescence imaging. For drug screening, select antiviral compounds including interferon beta 1 (IFN1), ribavirin, pyrrolidine dithiocarbamate (PDTC), and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of some of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with the reported drug effects in previous studies. Finally, mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways within these hiPSC-CMs after IFN1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to confirm antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that could be used to screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion.
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 4000
Description
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown. Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging. ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions. These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity. Overall design: Immortalized brown/beige-like preadipocyte cell line(iBAd Cells) was used for ATAC-Seq and mRNA-Seq. For RNA-Seq, triplicate experiments were performed, for ATAC-Seq individual samples were sequenced after 5 days of differentiation with either control treatment, or including IL-10 overnight prior to addition of Isoproterenol for 5-6 hours. Inguinal White adipose tissue was used for RNA-Seq from either WT or IL-10-/- animals, where 11 IL10-/- mice and 9 WT mice were seperately pooled for library construction and sequencing.
Publication Title
IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 872 Downloadable Samples
Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 439 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
Identify genes in the gonadal adipose tissue whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 433 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
Identify genes in the liver whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished LXR-dependent induction of DC chemotaxis. Using the LDLR-/- mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for efficient emigration of DCs in response to chemotactic signals during inflammation.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse BMDCs were differentiated from bone marrow by GM-CSF and IL-4 for 9 days.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples