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GSE27962
Sus scrofa
16 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine.
Publication Title
Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Small molecule BET bromodomain inhibitors (BETi) are actively being pursued in clinical trials for the treatment of a variety of cancers, however, the mechanisms of resistance to targeted BET protein inhibitors remain poorly understood. Using a novel mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BET inhibitor treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi, JQ1. Through application of Multiplexed Inhibitor Beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BET inhibitor therapy. Overall design: RNAseq was employed to identify changes in kinase RNA expression following short term (48h) or chronic (JQ1R) JQ1 treatment in three different ovarian cancer cell lines.
Publication Title
Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 157 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Information about the genes that are preferentially expressed during the course of Alzheimers disease (AD) could improve our understanding of the molecular mechanisms involved in the pathogenesis of this common cause of cognitive impairment in older persons, provide new opportunities in the diagnosis, early detection, and tracking of this disorder, and provide novel targets for the discovery of interventions to treat and prevent this disorder. Information about the genes that are preferentially expressed in relationship to normal neurological aging could provide new information about the molecular mechanisms that are involved in normal age-related cognitive decline and a host of age-related neurological disorders, and they could provide novel targets for the discovery of interventions to mitigate some of these deleterious effects.
Publication Title
Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone. AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory, reasoning, and often aberrant behaviors that are seen in patients with AD. Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression. A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies."
Publication Title
Gene expression correlates of neurofibrillary tangles in Alzheimer's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 107 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Gene expression was analysed in the colon and brain of normal rat pups from late prenatal through early postnatal development. Tissue was isolated from pups one day prior to the anticipated date of birth and throughout the suckling period until the end of weaning.
Publication Title
Sialic acid utilisation and synthesis in the neonatal rat revisited.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Preimplantation Genetic Testing (PGT), which encompasses both Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS), is a form of prenatal screening done on embryos conceived through assisted reproduction techniques (ART) prior to the initiation of pregnancy to ensure that only select embryos are used for transfer. PGT is typically performed on 8-cell embryos derived from either in vitro fertilization or intracytoplasmic sperm injection (ICSI) followed by extended culture. PGT requires a highly invasive embryo biopsy procedure that involves 1) incubating embryos in divalent-cation-deficient medium to disrupt cell adhesion, 2) breaching the protective zona pellucida with acid Tyrodes, laser drilling, or mechanical force and 3) aspirating one or two blastomeres. In this study we developed a mouse model of the embryo biopsy procedure inherent to PGT to determine the effect of various aspects of the procedure (incubation in Ca2+/Mg2+-free medium (CMF), acid Tyrodes treatment, blastomere aspiration), performed individually or in combination, on global patterns of gene expression in the resulting blastocysts.
Publication Title
The effect of blastomere biopsy on preimplantation mouse embryo development and global gene expression.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of gene expression by RNA-seq upon siRNA mediated knockdown of scaffold attachment factor A (SAF-A) versus control siRNA in RPE1 cells at 24 hour and 48 hour time points post transfection reveals SAF-A loss does not impact on gene transcription Overall design: Two control RNA-seq libraries where produced (24h and 48h) to compare to the two SAF-A siRNA knockdown RNA-seq libraries, each was a single experimental replicate.
Publication Title
SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Most differentiation protocols for generation of hepatocyte-like cells from iPS cells generate cells with heterogenous expression of hepatic markers, which confounds results from liver disease models involving complex traits and subtle phenotypes
Publication Title
Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity.
Publication Title
Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells.
Sample Metadata Fields
No sample metadata fields
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