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GSE36004
Homo sapiens
3 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Osteosarcomas are the most common primary malignant tumours of bone, and almost all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. The cell lines showed complex patterns of DNA copy number changes, where copy number gains were significantly associated with gene-rich regions of the genome and losses with gene-poor areas. Integration of the datasets showed that the mRNA levels were regulated by either alterations in DNA copy number or DNA methylation. Using a recurrence threshold of 6/19 (> 30 %) cell lines, 348 genes were identified as having alterations of two data types (gain or hypo-methylation/over-expression, loss or hyper-methylation/under-expression). These genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2-deoxycytidine treatment for all four genes tested. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for some genes. Integrative analysis of genome-wide genetic and epigenetic alterations identified mechanistic dependencies and relationships between DNA copy number and DNA methylation in terms of regulating mRNA expression levels in osteosarcomas, contributing to better understanding of osteosarcoma biology.
Publication Title
Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The role of RB1 in response to radiation was examined in human osteoblasts. We demonstrate that RB1 induced SASP genes, a response which was attenuated in RB1 knockdown osteoblasts.
Publication Title
Immune response to RB1-regulated senescence limits radiation-induced osteosarcoma formation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated bipolar patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD.
Publication Title
Utilization of never-medicated bipolar disorder patients towards development and validation of a peripheral biomarker profile.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Irritant contact dermatitis (ICD) pathogenesis is not completely understood and the genes participating in the epidermal response towards chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies (, 4 and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to sodium lauryl sulphate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays revealed essentially different pathway responses h after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen activated signalling cascades including ERK and growth factor receptor signalling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed while 26 suggested common biomarkers were identified . In conclusion, we bring new insights into two hitherto less well elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative exposure, respectively.
Publication Title
Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To obtain a separation of the epidermal and dermal compartments in order to examine compartment specific biological mechanisms in the skin we incubated 4 mm human skin punch biopsies in ammonium thiocyanate (NH4SCN). We wanted to test 1) the histological quality of the dermo-epidermal separation obtained by different incubation times 2) the amount and quality of extractable epidermal RNA, and 3) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30 minutes incubation, the split between dermis and epidermis was not always histologically well-defined (i.e. occurred partly intra-epidermally) but varied between subjects. Consequently, curettage along the dermal surface of the biopsy was added to the procedure. This modified method resulted in an almost perfect separation of the epidermal and dermal compartments and satisfactory amounts of high-quality RNA were obtained. Hybridization to Affymetrix HG_U133A 2.0 GeneChips showed that ammonium thiocyanate incubation had a minute effect on gene expression resulting in only one significantly downregulated gene (cystatin E/M). We conclude that epidermis can be reproducibly and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove valuable in the many different settings, where the epidermal and dermal compartments need to be evaluated separately.
Publication Title
Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Missense mutations in the gene for the ubiquitously expressed superoxide dismutase-1 (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease in humans killing selectively large motor neurons. Mice and rats overexpressing mutant SOD1 develop an adult onset neurodegenerative disease with hindlimb-paralysis and subsequent death similar to the human condition. In order to analyze the effects of mutant SOD1 expression onto the most affected cell-type in ALS, a small subpopulation of spinal cord cells, we propose to use laser microdissection to isolate mouse lumbar motor neurons and to assess the changes onto the mRNA expression profile using Affymetrix GeneChips compared to control animals. While two studies applying a genomic approach on the ALS mouse models used the entire spinal cord, contributions of changes to motor neurons were masked by the inflammatory effects of mutant SOD1 and the much larger population of non-motor neuronal cells. What is therefore needed is a cell-type specific expression profile that could reveal dysregulations in the transcriptome of the affected motor neurons.
Publication Title
Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Metal tolerance is often a result of metal storage or distribution. Thus, with the goal of advancing the molecular understanding of such metal homeostatic mechanisms, natural variation of metal tolerance in Arabidopsis thaliana was investigated. Substantial variation exists in tolerance of excess copper (Cu), zinc (Zn) and cadmium (Cd). Two accessions, Col-0 and Bur-0, and a recombinant inbred line (RIL) population derived from these parents were chosen for further analysis of Cd and Zn tolerance variation, which is evident at different plant ages in various experimental systems and appears to be genetically linked. Three QTLs, explaining in total nearly 50 % of the variation in Cd tolerance, were mapped. The one obvious candidate gene in the mapped intervals, HMA3, is unlikely to contribute to the variation. In order to identify additional candidate genes the Cd responses of Col-0 and Bur-0 were compared at the transcriptome level. The sustained common Cd response of the two accessions was dominated by processes implicated in plant pathogen defense. Accession-specific differences suggested a more efficient activation of acclimative responses as underlying the higher Cd tolerance of Bur-0. The second hypothesis derived from the physiological characterization of the accessions is a reduced Cd accumulation in Bur-0.
Publication Title
Natural variation in Arabidopsis thaliana Cd responses and the detection of quantitative trait loci affecting Cd tolerance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions. This dynamic alteration in nucleosome structure provides a molecular mechanism to regulate transcription. Here we analysed the transcription profiles of single and double mutants and wild-type cells by whole-genome microarray analysis. Our results indicate that genome-wide transcriptional misregulation in htz1 can be partially or totally suppressed if SWR1 is not formed (swr1), if it forms but cannot bind to chromatin (swc2), or if it binds to chromatin but has no histone replacement activity (swc5). These results suggest that in htz1 the nucleosome remodelling activity of SWR1 affects chromatin integrity because of an attempt to replace H2A with Htz1 in the absence of the latter.
Publication Title
The SWR1 histone replacement complex causes genetic instability and genome-wide transcription misregulation in the absence of H2A.Z.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development.
Publication Title
Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples