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GSE69554
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified DCIR2+DCs but not DEC205+DCs as able to induce peripheral T cell tolerance in pre-diabetic autoimmune NOD mice. To determine what distinct genetic programs are elicited in the auto-reactive CD4 T cells early after stimulation by these two DC subsets, we utilized adoptive transfer of BDC2.5 CD4 T cells into NOD mice, which were then given chimeric antibody to deliver the beta-cell specific antigen to either DCIR2+DCs or DEC205+DCs, leading to BDC2.5 CD4 T cell specific stimulation in vivo. The analysis shows that the negative transcriptional factor Zbtb32 (ROG) is up-regulated more in BDC2.5 CD4 T cells after stimulated with a antigen via DCIR2+DCs presentation, compared with DEC205+DCs, suggesting the involvement of Zbtb32 in DCIR2+DCs-mediated auto-reactive T cell tolerance in disease ongoing NOD mice.
Publication Title
DCIR2+ cDC2 DCs and Zbtb32 Restore CD4+ T-Cell Tolerance and Inhibit Diabetes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Spleen conventional dendritic cells from NOD mice show a lower overall response to CpG-A compared to B6 cDCs.
Publication Title
Despite Increased Type 1 IFN, Autoimmune Nonobese Diabetic Mice Display Impaired Dendritic Cell Response to CpG and Decreased Nuclear Localization of IFN-Activated STAT1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
NextSeq 500
Description
Maintaining cell fate relies on robust mechanisms that prevent the differentiation of specified cells into other cell types. This is especially critical during embryogenesis, when extensive cell proliferation, patterning and migration events take place. Here we show that vertebrate primordial germ cells (PGCs) are protected from reprogramming into other cell types by the RNA-binding protein Dead end (Dnd). PGCs knocked down for Dnd lose their characteristic morphology and adopt that of various somatic cell types. Concomitantly, they gain a gene expression profile reflecting differentiation into cells of different germ layers, in a process that we could direct by expression of specific cell-fate determinants. Importantly, we visualized these events within live zebrafish embryos, which provide temporal information regarding cell reprogramming. Our results shed light on the mechanisms controlling germ cell fate maintenance and are relevant for the formation of teratoma, a tumor class composed of cells from more than one germ layer. Overall design: Transcriptome profiling of 13hpf sorted germ cells of zebrafish embryos injected with either control or dead end Morpholino
Publication Title
The Vertebrate Protein Dead End Maintains Primordial Germ Cell Fate by Inhibiting Somatic Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Humoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Publication Title
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Publication Title
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
assess the efficacy of Pimasertib to characterize its mechanism of action
Publication Title
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling rapidly shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol, and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. Overall design: shRNA to SREBF1 (shSREBP1) or SREBF2 (shSREBP2) were stably introduced via 3rd generation lentivirus into human THP1 monocytic cells under puromycin selection. Non-targeting shRNA scramble was used for a control (shControl). shControl, shSREBP1 and shSREBP2 modified cell types were analyzed by RNA-seq in duplicate.
Publication Title
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling.
Sample Metadata Fields
No sample metadata fields
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