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SRP075467
Homo sapiens
221 Downloadable Samples
Illumina HiSeq 2500
Description
Here we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Publication Title
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. Overall design: Duct cells were isolated from mice of 3 different genotypes and duct cells from 3 mice of each genotype were sequenced. For the put back experiments, control retrovirus and that expressing Brg1 were transdcued in Brg1 null IPMN mouse cell line.
Publication Title
Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500
Description
In response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2a (eIF2a-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2a-P cytoprotection in response to UVB. Loss of eIF2a-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2a-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2a-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5'-leader of CDKN1A mRNA. We conclude that eIF2a-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. Overall design: Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.
Publication Title
Translational control of a human <i>CDKN1A</i> mRNA splice variant regulates the fate of UVB-irradiated human keratinocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 61 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Publication Title
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Purpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload.
Publication Title
Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP.
Publication Title
Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
Publication Title
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial.
Publication Title
Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
To improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions. The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes. These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies. Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs. Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes. Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13. Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Overall design: Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.
Publication Title
Expression and functions of long noncoding RNAs during human T helper cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples