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GSE47452
Mus musculus
36 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Here, we examined mouse brain trancriptional changes 1 hour after the 10th daily i.p. treament with one of the four following treaments: i) vehicle control (45% saline, 45% PEG-400 and 10% DMSO administered at 7.5mL/kg), ii) Cpd-60, 45mg/kg , administered at 7.5mL/kg or iii) SAHA, 25mg/kg, administered at 5mL/kg) or iv) CI-994, 10mg/kg, administered at 5mL/kg. Cpd-60 is a benzamide HDAC inhibitor with selectivity for class I HDAC subtypes HDAC1 and HDAC2; CI-994 is a benzamide inhibitor with selectivity for HDACs1,2 and 3; SAHA is a hydroxamic acid HDAC inhibitor with selectivity for class I HDAC subtypes 1,2, and 3 and the class II HDAC subtype HDAC 6. We examined transcript differences using the Illumnia WG-6 2.0 whole genome expression array and profiled 3 specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from each of 36 mice (n=6 mice / treatment group) . For application to array chips, we pooled two biological replicates from like treatment and brain region-groups such that 36 samples were applied in total: 4 treatment groups x 3 brain regions per treament group x 3 pools of two samples each for each treatment/brain region.
Publication Title
A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
HaCat cell cycle experiment: During the somatic cell cycle, DNA and epigenetic modifications in DNA and histones are copied to daughter cells. DNA replication timing is tightly regulated and linked to GC content, chromatin structure, andgene transcription, but how maintenance of histone modifications relates to replication timing and transcription is less understood.The gene expression patters on HaCaT keratinocytes during the cell cycle is studied by a time series analysis of synchroniced cells sampled at 3 hour intervals. We show that genes enriched with the repressive chromatin mark histone H3 lysine 27 tri-methylation are transcribed during DNA replication . The gene expression is related to replication timing, as genes expressed during G1/S transition andearly S phase generally have higher GC content and are replicated earlier than genes expressed during late S phase. These results indicate widespread replication-dependent expression in mammals and support a role for replication in transiently activating transcription of epigenetically silenced genes.
Publication Title
Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Pan troglodytes, Homo sapiens
- 355 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells. These cell lines have been used to search for genetic variants that are associated with drug response as well as with more basic cellular traits such as RNA levels. In setting out to extend such studies by searching for genetic variants contributing to drug response, we observed that phenotypes in LCLs were, in our lab and others, significantly affected by experimental confounders (i.e. in vitro growth rate, metabolic state, and relative levels of the Epstein-Barr virus used to transform the cells). As we did not find any SNPs associated with genome-wide significance to drug response, we evaluated whether incorporating RNA expression levels (and eQTLs) in the analysis could increase power to detect such effects. As previously shown, cis-acting eQTLs were detectable for a sizeable fraction of RNAs and baseline levels of many RNAs predicted response to several drugs. However, we found only limited evidence that SNPs influenced drug response through their effect on expression of RNA. Efforts to use LCLs to map genes underlying cellular traits will require great care to control experimental confounders, unbiased methods for integrating and interpreting such multi-dimensional data, and much larger sample sizes than have been applied to date.
Publication Title
Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 221 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In Huntingtons disease (HD), expanded HTT CAG repeat length correlates strongly with age at motor onset, indicating that it determines the rate of the disease process leading to diagnostic clinical manifestations. Similarly, in normal individuals, HTT CAG repeat length is correlated with biochemical differences that reveal it as a functional polymorphism. Here, we tested the hypothesis that gene expression signatures can capture continuous, length-dependent effects of the HTT CAG repeat. Using gene expression datasets for 107 HD and control lymphoblastoid cell lines, we constructed mathematical models in an iterative manner, based upon CAG correlated gene expression patterns in randomly chosen training samples, and tested their predictive power in test samples. Predicted CAG repeat lengths were significantly correlated with experimentally determined CAG repeat lengths, whereas models based upon randomly permuted CAGs were not at all predictive. Predictions from different batches of mRNA for the same cell lines were significantly correlated, implying that CAG length-correlated gene expression is reproducible. Notably, HTT expression was not itself correlated with HTT CAG repeat length. Taken together, these findings confirm the concept of a gene expression signature representing the continuous effect of HTT CAG length and not primarily dependent on the level of huntingtin expression. Such global and unbiased approaches, applied to additional cell types and tissues, may facilitate the discovery of therapies for HD by providing a comprehensive view of molecular changes triggered by HTT CAG repeat length for use in screening for and testing compounds that reverse effects of the HTT CAG expansion.
Publication Title
Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 195 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify a prognostic gene signature accounting for the distinct clinical outcomes in ovarian cancer patients
Publication Title
A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.
Sample Metadata Fields
Specimen part, Disease stage, Cell line, Treatment
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To demonstrate the use of a whole-genome oligonucleotide array to perform expression profiling on a series of microdissected late-stage, high-grade papillary serous ovarian adenocarcinomas to establish a prognostic gene signature correlating with survival and to identify novel survival factors in ovarian cancer.
Publication Title
A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 61 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Induced pluripotent stem cells (iPSCs) can be generated by enforced expression of defined transcription factors in somatic cells. It remains controversial whether iPSCs are equivalent to blastocyst-derived embryonic stem cells (ESCs). Using genetically matched cells, we found that the overall mRNA expression patterns of these cell types are indistinguishable with the exception of a few transcripts encoded on chromosome 12qF1.
Publication Title
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar.
Publication Title
Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples