The purpose of this study is to understand the effects of adrenergic signaling on the transcriptome of cell line models postulated to be the cells of origin of epithelial ovarian cancers using RNA-Seq. Here we explored the effects of the stress-related hormone, norepinephrine, on normal human ovarian and fallopian tube surface epithelial cellss. We investigated the early transcriptional response to norepinephrine in normal immortalized ovarian surface epithelial cells and fallopian tube secretory cells. RNA-Seq data of treated and untreated cells were analyzed to identify genes with differential expression. Overall design: RNA-seq data from ovarian surface epithelial cells and fallopian tube epithelial cells after treatment with 1µM norepinephrine for 1 hour (or mock-treatment). Three independent replicates were performed for each condition and cell line.
Early transcriptional response of human ovarian and fallopian tube surface epithelial cells to norepinephrine.
Specimen part, Cell line, Treatment, Subject
View SamplesOvarian cancer is the fifth most common form of cancer in women in the United States. Among different types of ovarian cancer, epithelial ovarian cancer is the most common and is highly lethal, however, prognostic and predictive markers, which can be used to predict chemoresponse and patient survival, have not been thoroughly explored. One critically important yet often overlooked component to the tumor progression process is the tumor microenvironment. Primarily composed of fibroblasts and extracellular matrix proteins (ECM) as well as endothelial cells and lymphocytic infiltrate, the tumor microenvironment has been shown to directly affect cell growth, migration, and differentiation through secreted proteins, cell-cell interactions and matrix remodeling (Tlsty and Coussens, 2006). The tumor microenvironment has the potential to promote tumor initiation of normal epithelial cells and facilitate progression of malignant cells, thereby, presenting a unique approach to diagnosing, understanding and treating cancer. Using a whole-genome oligonucleotide array platform to perform transcriptome profiling on the fibroblastic stromal component microdissected from a series of advanced stage high-grade serous ovarian adenocarcinomas, we identified a transcriptome signature for the ovarian cancer associated fibroblast (CAF). We further functionally characterized one of the identified genes, MFAP5, and we showed that stromal MFAP5 is a prognostic marker associated with poor patient survival. In addition to that, to investigate the signaling machanism and the effect of MFAP5 treatment on ovarian cancer cells, transcriptome profiling of MFAP5 treated OVCA432 high-grade serous ovarian cancer cells was performed. Further functional studies showed that stromal MFAP5 modulated ovarian cancer cell motility and invasion potential.
Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.
Cell line
View SamplesWhile VEGF-targeted therapies are showing promise in clinical studies, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homologue 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation and indicates the presence of a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin 1 (VASH1). EZH2 silencing in the tumor-associated endothelial cells resulted in inhibition of angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth. Combined, these data provide a new understanding of the regulation of tumor angiogenesis and support the potential for targeting EZH2 as a novel therapeutic approach.
Regulation of tumor angiogenesis by EZH2.
No sample metadata fields
View SamplesStrain differences in gene expression in the hypothalamus of BXD recombinant inbred mice
Sex-specific modulation of gene expression networks in murine hypothalamus.
Sex, Age, Specimen part
View SamplesThis dataset describe the transcriptomic profiling of adult brain, gonades (testis and ovaries) of adult zebrafish exposed to 20µg/L of depleted uranium for 10 days. The progeny of the exposed fishes were also analysed at two-cells stage and 96 hours post fertilization Overall design: Biological samples (adult dissected tissues and whole embryos and larvae) were tested by RNASeq in duplicates
Whole transcriptome data of zebrafish exposed to chronic dose of depleted uranium.
No sample metadata fields
View SamplesApproximately 2.5 mg dry Col-0 seedlings were surface sterilized and stratified for 2 days at 4degreesC in liquid media containing 1.5% sucrose (w/v) before being transferred to light with constant shaking at 100 rpm on an orbital shaker. After 7 days, the seedling clusters were subjected to the treatments for 1 hr followed by total RNA isolation using the RNAqueous kit (Ambion). Each treatment was performed in triplicate or quadruplicate. All labeling (Enzo) and hybridization (Affymetrix) procedures were performed as directed by the manufacturers. Raw probe intensities output by the Affymetrix MAS software were processed using the RMA algorithm to obtain an expression measure for each gene on each array.
Identification of inhibitors of auxin transcriptional activation by means of chemical genetics in Arabidopsis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
View SamplesLeukemia stem cells (LSCs) are an attractive target in treatment of many types of blood cancers. There remains an incomplete understanding of the epigenetic mechanisms driving LSC formation and maintenance, and how this compares to the epigenetic regulation of normal hematopoietic stem cells (HSCs).
Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains.
Specimen part
View SamplesWe used microarrays to detail the differentail gene expression between intestinal Lgr5(hi) stem cells and differentiated cells
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
View SamplesTransplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the effective dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4C, 10M dmPGE2, 60 minutes). Incubation conditions were identified (37C, 10M dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View Samples