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GSE21687
Mus musculus, Homo sapiens
275 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genomic technologies have unmasked molecularly distinct subgroups among tumors of the same histological type; but understanding the biologic basis of these subgroups has proved difficult since their defining alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher complex genomic data sets by matching the genetic alterations contained within these, with candidate cells of origin, to generate accurate disease models. Using an integrated genomic analysis we first identified subgroups of human ependymoma: a form of neural tumor that arises throughout the central nervous system (CNS). Validated alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. Matching the transcriptomes of human ependymoma subgroups to those of distinct types of mouse radial glia (RG)neural stem cells (NSCs) that we identified previously to be a candidate cell of origin of ependymoma - allowed us to select RG types most likely to represent cells of origin of disease subgroups. The transcriptome of human cerebral ependymomas that amplify EPHB2 and delete INK4A/ARF matched most closely that of embryonic cerebral Ink4a/Arf-/- RG: remarkably, activation of EphB2 signaling in this RG type, but not others, generated highly penetrant ependymomas that modeled accurately the histology and transcriptome of one human cerebral tumor subgroup (subgroup D). Further comparative genomic analysis revealed selective alterations in the copy number and expression of genes that regulate neural differentiation, particularly synaptogenesis, in both mouse and human subgroup D ependymomas; pinpointing this pathway as a previously unknown target of ependymoma tumorigenesis. Our data demonstrate the power of comparative genomics to sift complex genetic data sets to identify key molecular alterations in cancer subgroups.
Publication Title
Cross-species genomics matches driver mutations and cell compartments to model ependymoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 7 Downloadable Samples
Illumina humanRef-8 v2.0 expression beadchip, Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 7 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip, Illumina HumanRef-8 v3.0 expression beadchip
Description
Results of blocking the HER-2 oncogene kinase function in SUM-225 cells by treatment with CP724,714 and measuring gene expression as a function of time provides information as to what genes are regulated by HER-2 in this breast cancer cell line.
Publication Title
Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina HiSeq 4000
Description
Purpose: The objective of this study was to determine cardiac transcriptional pathways regulated in response to 1.) hypothyroidism and re-establishment of a euthyroid state and 2.) Med13-dependent cardiac transcriptional pathways regulated in response to hypothyroidism and re-establishment of a euthyroid state Overall design: Methods: WT and Med13 cardiac-specific knockout mice (Med13cKO) were put on a normal chow or PTU diet at 8 weeks of age for a duration of 4 weeks. A third group was put on a PTU diet for 4 weeks followed by 3 daily injections of T3.
Publication Title
Regulation of cardiac transcription by thyroid hormone and Med13.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The transcriptomic profiling of psoriasis has led to an increased understanding of disease pathogenesis. Although microarray technologies have been instrumental in this regard, it is clear that these tools detect an incomplete set of DEGs. RNA-seq can be used to supplement these prior technologies. Here, the use of RNAseq methods substantially increased the number of psoriasis-related DEGs. Furthermore, DEGs that were uniquely identified by RNA-seq, but not in other published microarray studies, further supported the role of IL-17 and tumor necrosis factor-a synergy in psoriasis. Examination of one of these factors at the protein level confirmed that RNA-seq is a powerful tool that can be used to identify molecular factors present in psoriasis lesions, and may be useful in the identification of therapeutic targets that to our knowledge have not been reported previously. Further studies are in progress to determine the biological significance of DEGs uniquely discovered by RNA-seq. Overall design: To define the transcriptomic profile of psoriatic skin, three pairs of lesional and nonlesional skin biopsy specimens were taken from patients with untreated moderate-to-severe plaque psoriasis.
Publication Title
Transcriptional profiling of psoriasis using RNA-seq reveals previously unidentified differentially expressed genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes.
Publication Title
Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 13 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The increased -smooth muscle-actin positive cancer-associated fibroblastic cells (CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients
Publication Title
Novel organotypic culture model of cholangiocarcinoma progression.
Sample Metadata Fields
Specimen part, Disease
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Validation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer.
Publication Title
Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Snt2 is a yeast chromatin-interacting protein whose function has not been well characterized, that was recently shown to associate with Ecm5 and the Rpd3 deacetylase. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we show that in response to H2O2, Snt2 and Ecm5 colocalize to promoters of genes involved in various aspects of the environmental stress response. By integrating these ChIP-seq results with expression analysis, we identify a key set of target genes that require Snt2 for proper expression after H2O2 stress. Finally, by mapping Snt2 and Ecm5 localization before and after rapamycin treatment, we identify a subset of H2O2-specific Snt2 and Ecm5 target promoters that are also targeted in response to rapamycin. Our results establish a function for Snt2 in regulating transcriptional changes in response to oxidative stress, and suggest Snt2 may have a role in additional stress pathways. Overall design: RNA-seq analysis to look at gene expression levels in wild-type, snt2 deletion, or ecm5 deletion strains before or 0.5 hours after treatment with H2O2 (final concentration 0.4 mM). This sequencing was done on biological triplicate samples.
Publication Title
The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 9 Downloadable Samples
- IlluminaHiSeq2500
Description
RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish Overall design: Embryos derived from a zic2aGBT133/+; zic2bUW1127/+ incross were sorted by presence or absence of coloboma. RNA was prepared from each individual embryo at ~ 25 hpf
Publication Title
Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples