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SRP089712
Mus musculus
86 Downloadable Samples
Illumina HiSeq 2000
Description
We analyzed Purkinje cell transcriptome dynamics in the developing mouse cerebellum during the first three postnatal weeks, a key developmental period equivalent to the third trimester in human cerebellar development. Our study represents the first detailed analysis of developmental Purkinje cell transcriptomes and provides a valuable dataset for gene network analyses and biological questions on genes implicated in cerebellar and Purkinje cell development. Overall design: Laser capture microdissection was employed to obtain a highly enriched population of cerebellar Purkinje cells. Deep sequencing was performed on RNA isolated from 1000 Purkinje cells at five developmental timepoints (postnatal days P0, P4, P8, P14 and P21) in triplicate.
Publication Title
A gene expression signature in developing Purkinje cells predicts autism and intellectual disability co-morbidity status.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
The combined influence of oncogenic drivers, genomic instability, and/or DNA damage repair deficiencies increases replication stress in cancer. Cells with high replication stress rely on the upregulation of checkpoints like those governed by CHK1 for survival. Previous studies of the CHK1 inhibitor prexasertib demonstrated activity across multiple cancer types. Therefore, we sought to (1) identify markers of prexasertib sensitivity and (2) define the molecular mechanism(s) of intrinsic and acquired resistance using preclinical models representing multiple tumor types. Our findings indicate that while cyclin E dysregulation is a driving mechanism of prexasertib response, biomarkers associated with this aberration lack sufficient predictive power to render them clinically actionable for patient selection. Transcriptome analysis of a pan-cancer cell line panel and in vivo models revealed an association between expression of E2F target genes and prexasertib sensitivity and identified innate immunity genes associated with prexasertib resistance. Functional RNAi studies supported a causal role of replication fork components as modulators of prexasertib response. Mechanisms which protect cells from oncogene-induced replication stress may safeguard tumors from such stress induced by a CHK1 inhibitor, resulting in acquired drug resistance. Furthermore, resistance to prexasertib may be shaped by innate immunity.
Publication Title
A pan-cancer transcriptome analysis identifies replication fork and innate immunity genes as modifiers of response to the CHK1 inhibitor prexasertib.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 57 Downloadable Samples
- Illumina HiSeq 2000
Description
Expression profiling by high throughput sequencing Overall design: 23 Tumor samples were obtained from a Sleeping Beauty forward genetic screen and sequenced using Illumina HiSeq 2000
Publication Title
<i>Sleeping Beauty</i> Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins.
Publication Title
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Publication Title
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 41 Downloadable Samples
- IonTorrentProton
Description
Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment. Overall design: Vehicle control, diclofenac, and three doses of the test compound (small-molecule neurotransmitter receptor antagonist) were applied to three primary cell lines, with three biological replicates in each group. In some treatment groups read-outs were only available for two samples. All together 41 samples were profiled.
Publication Title
Pathway reporter genes define molecular phenotypes of human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We report that colon adenomas from ApcMin/+ mice not only exhibit similarities in gene expression profile to colon adenomas from azoxymethane / dextran sulfate sodium-treated mice (with activating Ctnnb1 mutations) due to the activation of canonical WNT signaling, but also unique transcriptional changes in the pathways regulating cell cycle progression / proliferation, chromosome segregation / cytoskeletal organization and apoptosis. Subsequent experiments characterized changes in gene expression unique to colon adenomas from ApcMin/+ mice including increases in the H2afv, Map6 and Nsmf transcripts. Overall design: Examination of gene expression profiles in 2 different colon adenoma types with activated canonical WNT signaling, relative to their respective non-adenoma controls
Publication Title
Mutational Mechanisms That Activate Wnt Signaling and Predict Outcomes in Colorectal Cancer Patients.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing antisense oligonucleotides in mice
Publication Title
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing an antisense oligonucleotide in mice
Publication Title
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples