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GSE70918
Rattus norvegicus
4 Downloadable Samples
Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Tendon is a hypocellular tissue that contains functional cable-like units of type I collagen responsible for the transmission of force from muscle to bone. In the setting of injury or disease, patients can develop chronic tendinopathies that are characterized by pain, loss of function and persistent inflammatory changes that are often difficult to treat. Platelet-rich plasma (PRP) has shown promise in the treatment of chronic tendinopathy, but little is known about the mechanisms by which PRP can improve tendon healing. PRP contains many different growth factors and cytokines, and since these proteins can both activate and inhibit various signaling pathways it has been challenging to determine precisely which signaling pathways and cellular responses are most important. Using state-of-the-art bioinformatics tools and genome wide-expression profiling, the purpose of this study was to determine the signaling pathways activated within cultured tendon fibroblasts in response to PRP treatment.
Publication Title
Platelet-Rich Plasma Activates Proinflammatory Signaling Pathways and Induces Oxidative Stress in Tendon Fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
Illumina HiSeq 2000
Description
We examined context specific function of BRD4 in promoting lineage specific gene expression and show that BRD4 is essential for osteoblast differentiation. Overall design: We performed mRNA sequencing from hFOB cells (undifferentiated and differentiated for 5 days into osteoblastic lineage) following BRD4 inhibition by JQ1 or siRNA mediated depletion. The mRNA-Seq includes namely 7 conditions: undifferentiated hFOBs treated with DMSO or non-targeting control siRNA (siCNTR), differentiated hFOBs with DMSO or siCNTR treatments; differentiated hFOBs treated with JQ1 or two siRNAs against BRD4 (#3 & #4). The libraries were performed in triplicates.
Publication Title
BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
The estrogen receptor-a (ERa) is a transcription factor which plays a critical role in controlling cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to induce or repress gene transcription. A deeper understanding of these transcriptional mechanisms may uncover novel therapeutic targets for ERa-dependent cancers. Here we show for the first time that BRD4 regulates ERa-induced gene expression by affecting elongation-associated phosphorylation of RNA Polymerase II (RNAPII P-Ser2) and histone H2B monoubiquitination (H2Bub1). Consistently, BRD4 activity is required for estrogen-induced proliferation of ER+ breast and endometrial cancer cells and uterine growth in mice. Genome-wide occupancy studies revealed an enrichment of BRD4 on transcriptional start sites as well as EREs enriched for H3K27ac and demonstrate a requirement for BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we further demonstrate that BRD4 occupancy correlates with active mRNA transcription and is required for the production of ERa-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ERa function and potential therapeutic target. Overall design: mRNA expression profiles of MCF7 cells treated with +/- estrogen treatment under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.
Publication Title
Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Here we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of epithelial differentiation-specific genes. Interestingly, we show that BRD4 perturbation regulates the expression of Grainy Head-like transcription factor, GRHL3, whose depletion partially mimics BRD4 inhibition and blocks differentiated phenotype. By binding to the distal regions of GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of GRHL3 expression. Overall design: mRNA expression profiles of MCF10A cells under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.
Publication Title
BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor- (TNF-) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
Publication Title
Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.
Sample Metadata Fields
Sex, Specimen part, Race, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a CRC related signature of differentially expressed genes discriminating patients Responder and Non Responder to radiochemotherapy
Publication Title
A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We performed a microarray screening of adult rat retinas to identify genes that could show and up- or down-regulation due to exposure to light.
Publication Title
A component of retinal light adaptation mediated by the thyroid hormone cascade.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study seeks to understand the mechanisms behind enhanced lymphomagenesis observed in ImHABCL6/Uchl1 mice compared with ImHABCL6 alone. As the lymphomas arise from germinal center (GC) B-cells, we reasoned that transgenic Uchl1 altered the gene expression patterns in GC B-cells from these animals. We therefore isolated pre-malignant GC B-cells and examined the gene expression patterns to identify pathways affected by the addition of Uchl1.
Publication Title
UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Metzincins and related genes (MARGS) play important roles in ECM remodeling in fibrotic conditions.
Publication Title
Renal Fibrosis mRNA Classifier: Validation in Experimental Lithium-Induced Interstitial Fibrosis in the Rat Kidney.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Gene expression profiling leading to the identification of novel components in the EDS1/PAD4-regulated defence pathway
Publication Title
Salicylic acid-independent ENHANCED DISEASE SUSCEPTIBILITY1 signaling in Arabidopsis immunity and cell death is regulated by the monooxygenase FMO1 and the Nudix hydrolase NUDT7.
Sample Metadata Fields
Age, Specimen part, Time
View Samples