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GSE55917
Homo sapiens
5 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In acute myeloid leukemia (AML), leukemia stem cells (LSCs) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic regulation balances normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic modifiers are now considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis; however, the function of miRNA in LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly predictive of patient survival. Gain-of-function genetic analysis demonstrated that miR-126 restrained cell cycle progression, prevented LSC differentiation, and increased LSC self-renewal. miR-126 promoted chemo-resistance, preserving LSC quiescence in part through suppression of the G0-to-G1 gatekeeper, CDK3. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.
Publication Title
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Timps are natural metalloproteinase inhibitors that direct the cell microenvironment in health and disease, yet the essential requirement of this gene family in mammals is unknown. We generated quadruple Timp deficient mice lacking Timp1, Timp2, Timp3 and Timp4 (TIMPless) and found that Timp function is essential for postnatal lifespan, lung form and function and skeletogenesis. TIMPless mice survive embryogenesis but develop pervasive skeletal aberrations characterized by axial cartilage overgrowth and growth plate closure in long bones. We performed microarray analysis to identify signaling pathways affected by the loss of the entire Timp family in sternal cartilage.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
JMJD2B is expressed in a high proportion of human breast tumors, and the expression levels significantly correlate with estrogen receptor (ER) positivity. To assess the effect of JMJD2B depletion on the ER signaling pathway, we performed genome-wide gene expression analysis using the Affymetrix Human Gene 1.0 ST array.
Publication Title
Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Epigenetic modifications such as methylation silencing of genes with CpG-island-associated promoters is frequently observed in cancer. Studies regarding the implications of epigenetic modifications in osteosarcoma (OS) have been limited. The epigenetic drug decitabine is a potential re-activator of silenced genes through de-methylation, and is currently undergoing clinical trials for cancer treatment. No study to date has utilized decitabine to modify gene expression in OS-derived cells to identify gene-specific methylation targets that may have therapeutic importance. The objective of this study was to measure the response of the OS cell line, U-2OS, to decitabine treatment both in vitro and in vivo.
Publication Title
Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: identification of apoptotic genes as targets for demethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic hallmarks of localized, non-indolent prostate cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The size and scope of microarray experiments continue to increase. However, datasets generated on different platforms or at different centres contain biases. Improved techniques are needed to remove platform- and batch-specific biases. One experimental control is the replicate hybridization of a subset of samples at each site or on each platform to learn the relationship between the two platforms. To date, no algorithm exists to specifically use this type of control. LTR is a linear-modelling-based algorithm that learns the relationship between different microarray batches from replicate hybridizations. LTR was tested on a new benchmark dataset of 20 samples hybridized to different Affymetrix microarray platforms. Before LTR, the two platforms were significantly different; application of LTR removed this bias. LTR was tested with six separate data pre-processing algorithms, and its effectiveness was independent of the pre-processing algorithm. Sample-size experiments indicate that just three replicate hybridizations can significantly reduce bias. An R library implementing LTR is available.
Publication Title
LTR: Linear Cross-Platform Integration of Microarray Data.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
Publication Title
Genomic hallmarks of localized, non-indolent prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 69 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Microarray analysis revealed that changes in genes expressions are brain region-dependent; expression of several genes are affected by point mutation L100P, which was verified by RT-PCR (Lcn2, Cyr61, Slc6a12, Slc40a1, Egr2), a few genes are affected by genotype and valproate (Dusp1 and Purb), suggesting their role in valproate-induced benificial effect on sensorimotor gaiting in Disc1-L100P mutant mice. The final conclusion will be drawn after series of RT-PCR confirmation.
Publication Title
Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3.
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples- Mus musculus
- 65 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500g/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear.
Publication Title
Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD.
Sample Metadata Fields
Sex, Specimen part
View Samples