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SRP115022
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Activation of macrophages by inflammatory stimuli leads to reprogramming of mitochondrial metabolism to support the production of pro-inflammatory cytokines. Hallmarks of this metabolic rewiring are downregulation of a-ketoglutarate formation via isocitrate dehydrogenase (IDH) and accumulation of glutamine-derived succinate, which enhances the inflammatory response via the activity of succinate dehydrogenase (SDH). Here, we identify the nuclear receptor Nur77 (Nr4a1) as a key regulator of the pro-inflammatory metabolic switch in macrophages. Nur77-deficient macrophages fail to downregulate IDH expression and accumulate higher levels of succinate and other downstream TCA cycle metabolites in response to an inflammatory stimulus. Consequently, these macrophages produce more nitric oxide and pro-inflammatory cytokines in an SDH-dependent manner. In vivo, bone marrow Nur77 deficiency exacerbates atherosclerosis development and leads to increased systemic succinate levels. In conclusion, Nur77 supports an anti-inflammatory metabolic state in macrophages that protects against chronic inflammatory diseases such as atherosclerosis. Overall design: Gene expression profiling by RNA-seq was performed in triplicate in RAW264.7 mouse macrophage stable cell lines with doxycycline-inducible overexpression of HA-tagged NUR77 or GFP as control.
Publication Title
Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
Illumina mouse-6 v1.1 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina mouse-6 v1.1 expression beadchip
Description
Tissue macrophages from peritoneal cavity, lung, liver, spleen, small intestine and adipose tissue and M-CSF derived bone marrow derived macrophages (BMDMs) were determined for gene expression.
Publication Title
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
Analysis of whole genome expression changes in livers from wild type animals and animals with a liver specific transgenic over expression of Cyp7a1. Mice were given a chronic, repetitive administration of LPS for 7 days. Our prior analysis had indicated that inflammation suppresses Cyp7a1 and that this leads to accumulation of intermediates in the mevalonate biosynthesis pathway. Here, we hypothesized that over expression of Cyp7a1 would not affect the changes in transcriptional state due to chronic administration of LPS. We provide gene expression data which evaluates this question. Here we find that over expression of Cyp7a1 minimally alters the transcriptome of livers in an untreated state, and that it has small effects on the response to chronic LPS. Overall design: Total RNA isolated from livers of wild type and liver specific Cyp7a1 transgenic animals treated with or without recurrent, daily LPS injections (1.5mg/kg) for 7 days. There are two biological replicates per condition. Samples are a matrix of all conditions reported as FPKMs.
Publication Title
The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
BMDMs were stimulated with ATRA and/or omentum culture supernatant and gene expression was determined by Illumina microarray
Publication Title
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of whole genome expression changes in primary hepatocytes in response to chronic stimulation with inflammatory cytokines. We hypothesized that chronic treatment of primary hepatocytes with TNF would result in a reprogramming of the cell's transcriptome to improve adaptation to the presence of a chronic inflammatory stress. Here we provide expression analysis detailing genes upregulated, downregulated, and unchanged after 2 days of TNF treatment. We have included gene expression profiling of cells treated with TNF for 2 hours to help isolate the changes unique to chronic TNF treatment of primary hepatocytes.
Publication Title
The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Peritoneal macrophages from control and Mac-Gata6 KO (LysM-cre;Gata6-floxed) mice were determined for genome wide gene expression.
Publication Title
Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Heart ventricle tissue was harvested from Trex1/RAG2 DKO mice and from Trex1WT/RAG2KO littermate controls. RNA was extracted, and an Affymetrix Mouse 430 2.0 gene chip analysis was performed.
Publication Title
Trex1 prevents cell-intrinsic initiation of autoimmunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The inflammatory response initiated by microbial products signaling through Toll-like receptors (TLRs) of the innate immune system is essential for host defense against infection. Because inflammation can be harmful to host tissues, the innate response is highly regulated. Negative regulation of TLR4, the receptor for bacterial lipopolysaccharide (LPS), results in LPS tolerance, defined as hyporesponsiveness to repeated stimulation with LPS. LPS tolerance is thought to protect the host from excessive inflammation by turning off TLR4 signal, which then shuts down TLR-induced genes. However, TLR signaling induces hundreds of genes with very different functions. We reasoned that genes with different functions should have different requirements for regulation. Specifically, genes encoding proinflammatory mediators should be transiently inactivated to limit tissue damage, while genes encoding antimicrobial effectors, which directly target pathogens, should remain inducible in tolerant cells to protect the host from infection. Using an in vitro system of LPS tolerance in macrophages, here we show that TLR-induced genes may indeed be divided into two distinct categories based on their functions and regulatory requirements. Further, we show these distinct groups are regulated by gene-specific, and not signal-specific mechanisms.
Publication Title
Gene-specific control of inflammation by TLR-induced chromatin modifications.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
The transcriptional coactivator Yap promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. Here we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal expansion, as proliferation is counterbalanced by increased apoptosis. To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required. In response to liver injury, Yap drives clonal expansion, suppresses hepatocyte differentiation and promotes a progenitor phenotype. These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair. Overall design: Totally sixteen samples
Publication Title
Two-signal requirement for growth-promoting function of Yap in hepatocytes.
Sample Metadata Fields
No sample metadata fields
View Samples