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GSE52262
Homo sapiens
21 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It has been suggested that breast cancers are driven and maintained by a cellular subpopulation with stem cell properties. These breast cancer stem cells (BCSCs) mediate metastasis and by virtue of their resistance to radiation and chemotherapy, contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSC populations.
Publication Title
Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It has been suggested that breast cancers are driven and maintained by a cellular subpopulation with stem cell properties. These breast cancer stem cells (BCSCs) mediate metastasis and by virtue of their resistance to radiation and chemotherapy, contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSC populations.
Publication Title
Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Emerging evidence suggest that miRNAs play an essential role in self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here we demonstrate that mir-100 expression is related to cellular differentiation state with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline inducible lentivirus driving mir-100 expression, we found that mir-100 overexpression decreased breast cancer stem cells (BCSCs) and inhibited cancer cell proliferation in vitro and in mouse xenografts by targeting SMARCA5, SMARCD1 and BMPR2.
Publication Title
MicroRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant cell proliferation, a hallmark of most cancers, requires the escape from intrinsic antitumour barriers. Primary among these is the DNA damage response (DDR). In both cell culture-models and in early stages of tumorigenesis in vivo, activated oncogenes induce DNA replication stress and DNA double-strand breaks (DSBs), leading to DDR activation and p53-dependent apoptosis and/or senescence. The means by which tumour-initiating cells, also termed cancer stem cells (CSCs), circumvent this oncosuppressive response is unknown. Here we demonstrate that the ZEB1 transcription factor provides breast CSCs with the ability to withstand an aberrant mitogenic activity. Its forced expression in human mammary epithelial cells is sufficient to alleviate DNA replicative stress and to decrease the production of reactive oxygen species, an important contributor to DDR and oncogene-induced senescence. Consistently, human breast cancer cells with endogenous ZEB1 expression show two characteristic features: low levels of DSBs and DDR markers, reflecting mitigation of the DNA replication stress, and a low p53 mutation frequency, reflecting a weak selective pressure for inactivation. Using high-throughput sequencing analysis of controlled cellular models, we further demonstrate that ZEB1 delays the onset of structural chromosomal instability (CIN), a known consequence of replicative stress and prevents the emergence of chromosome 8p deletions and 8q amplifications, two prevalent abnormalities in high-grade breast cancers. Supporting these findings, ZEB1 expression discriminates human breast tumours by their copy number alterations (CNAs) and chromosome 8 aberrations. We propose that the tumorigenic potential of CSCs relies upon their unique capacity to tolerate oncogenic stimuli through the alleviation of DNA replication stress.
Publication Title
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 51 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Publication Title
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Early-passage (<10 passages) cultures of melanoma cells from metastatic lymph node lesions and normal adult melanocytes explanted in parallel from the adjacent, non-involved skin of 5 patients were compared by cDNA arrays. Differences between normal and neoplastic counterparts were then assessed upon adjustment for individual factors.
Publication Title
A melanoma immune response signature including Human Leukocyte Antigen-E.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brain transcriptional and epigenetic associations with autism.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Illumina HumanHT-12 V4.0 expression beadchip
Description
Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
Publication Title
Brain transcriptional and epigenetic associations with autism.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 22 Downloadable Samples
Illumina HiSeq 2500
Description
Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Overall design: Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
Publication Title
Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.
Sample Metadata Fields
No sample metadata fields
View Samples