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SRP114371
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- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 1500
Description
Consumption of walnuts has slowed breast cancer growth and/or reduced the risk of breast cancer in mice. The significantly reduced mean tumor size or numbers of tumors was associated with changing the expressions of many genes that are associated with cancer growth, survival and metastasis. Many women treated for breast cancer are interested in reducing the risk for recurrence. The study was a non-placebo, two-arm, clinical trial. Women with lumps large enough for research and pathology biopsies were recruited to the trial. One or two additional biopsies were taken for gene expression analyses using next generation RNA Sequencing methods. The subjects randomized to the walnut group immediately began to consume 2 ounces of walnuts per day until follow-up surgery, if surgery were needed. At follow up surgery, additional biopsies were taken from the surgically removed, cancerous tissue for additional gene expression analyses. Changes in gene expression compared to baseline were determined in tumors of each individual woman in walnut-consuming and control groups. Overall design: Gene expression profiles of two samples from each of ten breast cancer patients were obtained via RNA-Seq in a 2x50bp paired-end design. The first sample was obtained from biopsy; the second sample was taken at the time of surgery 2-3 weeks later. Five patients consumed two one-ounce packets of walnuts daily between the biopsy and surgery, while the other five remained on their regular diet.
Publication Title
Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 1500
Description
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). L-Type Amino Acid Transporter 1 (LAT1) is a leucine uptake transporter that is overexpressed in cancer. The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport. Overlapping the TCDD-RNA-Seq dataset in this report with a published TCDD-ChIP-seq dataset identified that LAT1 was a direct TCDD/AHR gene target. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR. TCDD-stimulated increases in LAT1 mRNA was also inhibited by the AHR antagonist CH-223191. Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD. In MDA-MB-231 cells, which exhibit high levels of endogenous AHR activity, the levels of endogenous LAT1 mRNA and protein were reduced in response to knockdown of AHR with AHR-siRNA. The regulation of LAT1 by AHR stimulated MDA-MB-231 proliferation. Collectively, these findings have provided a deeper mechanistic understanding of extrinsic and intrinsic regulation of LAT1 by AHR. Overall design: Expression profiling of four replicates of MCF-7 cells treated with 10nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq
Publication Title
Aryl hydrocarbon receptor (AHR) regulation of L-Type Amino Acid Transporter 1 (LAT-1) expression in MCF-7 and MDA-MB-231 breast cancer cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF--dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT. Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines. Functionally, GRHL2 suppressed TGF--induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF- receptor antagonist, BMP2. The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis. These results indicate that GRHL2 is a suppressor of the oncogenic EMT.
Publication Title
Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Leptin binding to the leptin receptor (LepR) causes rapid signaling to the nucleus. We investigated the early (2 hr) transcriptional response to acute leptin injection (intracerebroventricular)
Publication Title
Leptin Induces Mitosis and Activates the Canonical Wnt/β-Catenin Signaling Pathway in Neurogenic Regions of <i>Xenopus</i> Tadpole Brain.
Sample Metadata Fields
Treatment
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Leptin binding to the leptin receptor (LepR) causes rapid signaling to the nucleus. We investigated the early (2 hr) transcriptional response to acute leptin injectio (intracerebroventricular)
Publication Title
Ancient origins and evolutionary conservation of intracellular and neural signaling pathways engaged by the leptin receptor.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The intestinal immune system must elicit robust immunity against harmful pathogens but restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c macrophages in the lamina propria (LP) that express several anti-inflammatory molecules including interleukin 10 (IL-10), but little or no pro-inflammatory cytokines, even upon stimulation with Toll-like receptor (TLR) ligands. These macrophages induced, in a manner dependent on IL-10, retinoic acid and exogenous transforming growth factor-, differentiation of FoxP3+ regulatory T cells. In contrast, LP CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by LP macrophages, indicating that a dynamic interplay between these subsets may influence the balance between immune activation and tolerance.
Publication Title
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of inflammatory pathways in human IBD
Publication Title
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pathological bone changes differ considerably between inflammatory arthritic diseases, and most studies have focused on bone erosion. Collagen Induced Arthritis (CIA) is a model for Rheumatoid Arthritis, which, in addition to bone erosion, demonstrates bone formation at the time for clinical manifestations. The objective of this study was to use the CIA model to study bone remodelling by performing a gene expression profiling time-course study on the CIA model.
Publication Title
Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Etiolated Arabidopsis seedlings open their cotyledons and halt rapid elongation of hypocotyl when exposed to light (de-etiolation). Major light responsive components in this process have been identified and signaling pathways revealed, yet how the organ-specific light responses are achieved remains unknown. Here we report that a developmental regulator TCP4 (TEOSINTE BRANCHED1, CYCLOIDEA, and PCF) participates in photomorphogenesis and facilitates light-induced cotyledon-opening. We demonstrate that TCP4-like transcriptional factors, which predominantly express in cotyledons of both light and dark seedlings, activate SAUR16 and SAUR50 in response to light. Light repressor PIF3 (or PIFs, phytochrome-interacting factors), which accumulates in etiolated seedlings and rapidly declines upon light exposure, inhibits TCP4 promoter-binding and prevents activation of SAUR16/50 in darkness. Our study reveals how an interplay between light responsive factors and developmental regulators leads to signal-dependent and tissue-specific regulation of gene expressions, which ultimately resulted in organ-specific light responses during de-etiolation. Overall design: Cotyledon mRNA profiles of 4-day-old dark grown Col, mTCP4#4 and mTCP4#10 seedlings were generated by deep sequencing.
Publication Title
The Transcription Factors TCP4 and PIF3 Antagonistically Regulate Organ-Specific Light Induction of <i>SAUR</i> Genes to Modulate Cotyledon Opening during De-Etiolation in Arabidopsis.
Sample Metadata Fields
Specimen part, Subject
View Samples