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Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The NF-B pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic beta cell dysfunction in the metabolic syndrome. While canonical NF-B signaling is well studied, there is little information on the divergent non-canonical NF-B pathway in the context of pancreatic islet dysfunction in diabetes. Here, we demonstrate that pharmacological activation of the non-canonical NF-B inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. Further, we identify NIK as a critical negative regulator of beta cell function as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of non-canonical NF-B components p100 to p52, and accumulation of RelB. Tumor necrosis factor (TNF) and receptor activator of NF-B ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive beta cell intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the non-canonical NF-B transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to beta cell failure. These studies reveal that NIK contributes a central mechanism for beta cell failure in diet-induced obesity.
Publication Title
Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify the gene signature accounting for the distinct clinical outcomes in ovarian clear cell cancer patients
Publication Title
Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal1. In various pathophysiological conditions, erythrocyte life span is severely compromised, which threatens the organism with anemia and iron toxicity 2,3. Here we identify anon-demand mechanism specific to the liver that clears erythrocytes and recycles iron. We showthat Ly-6Chigh monocytes ingest stressed and senescent erythrocytes, accumulate in the liver, and differentiate to ferroportin 1 (FPN1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+ Tim-4neg macrophages are transient, reside alongside embryonically-derived Tim-4high Kuppfer cells, and depend on Csf1 and Nrf2. The spleenlikewise recruits iron-loaded Ly-6Chigh monocytes, but they do not differentiate into ironrecycling macrophages due to the suppressive action of Csf2, and are instead shuttled to the livervia coordinated chemotactic cues. Inhibiting this mechanism by preventing monocyte recruitment to the liver leads to kidney failure and liver damage. These observations identify the liver as the primary organ supporting emergency erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.
Publication Title
On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 1500
Description
Purpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases. Overall design: Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media). Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.
Publication Title
Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE1615- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects 5-10% of reproductive aged women. The hallmark characteristic of PCOS is increased ovarian androgen synthesis. Previous studies by our laboratory demonstrated that increased androgen synthesis is a stable biochemical phenotype of PCOS theca cells which are the primary source of ovarian androgen production. The increase in theca cell steroidogenesis was due to an increase in expression of several steroidogenic enzymes including CYP17 and CYP11A but not StAR. Interestingly, the anti-epileptic drug valproic acid induces increased theca cell androgen synthesis and increased CYP17 and CYP11A mRNA levels. In this study we have characterized the gene expression profiles of theca cells obtained from normal or polycystic ovaries which were maintained in the absence (UNT) or presence (VPA) of valproic acid. The data identifed new candidate genes and novel signaling pathways which may contribute to the manifestation of PCOS phenotypes including increased androgen production. The experiments in this study were carried using the Affymetrix U133A and U133B oligonucleotide chips.
Publication Title
Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
Publication Title
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Sca1+/cKit hematopoietic BMCs of hosts bearing primary tumors promote the growth of distant tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from old mice bearing primary tumors lack this ability
Publication Title
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the effects of recombinant granulin on human mammary stromal fibroblasts, we cultured immortalized GFP+ normal human mammary fibroblasts in the presence of recombinant human granulin (1ug/ml) or PBS every 24h for 6 days. To generate GRN-independent CAFs, we injected immortalized GFP+ human mammary fibroblasts, MCF7Ras human breast carcinoma cells, and 20% Matrigel subcutaneously into nude mice. Tumors were allowed to form for a period of 45 days. GFP+ fibroblasts were isolated from tumors by mincing the tumors, dissociating, and culturing in the presence of 1 ug/ml puromycin for ~3-4 weeks. CAF purity was confirmed by ensuring that 100% of the population was GFP-positive.
Publication Title
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This experiment is designed to detect genes differentially expressed in 2uM erlotinib treatment versus DMSO treatment and to identify differential gene set enrichments.
Publication Title
Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 34 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Proper regulation of nuclear factor B (NF-B) transcriptional activity is required for normal lymphocyte function, and deregulated NF-B signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-Binducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-B signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-B pathway in B lymphoproliferative disease.
Publication Title
Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation.
Sample Metadata Fields
No sample metadata fields
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