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GSE86861
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite education and aggressive treatment, breast cancer (BC) remains a clinical problem. BC cells (BCCs) can migrate early to metastatic sites where they may exist in cellular dormancy for decades. Presently, there are no consensus markers for cancer stem cells (CSCs) that are involved in tumor initiation and progression, and drug resistance. The current designation of CSCs might comprise similar tumor initiating cells, but at different developmental phase. In order to understand these differences, we developed a working hierarchy of BCCs. We initiated the studies in which three BCC subsets were selected based on the relative expressions of the stem cell-linked genes, Octamer4A (Oct4A). The sorted BCCs were subjected to array analyses using Affymetrix gene chip. Hierarchical clustering indicated distinct gene expression among the three subsets. Differential gene expressions of membrane proteins validated three novel genes, TMEM-98, GPR64 and FAT4. These three genes, in combination of known markers for CSCs, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1) and Oct4A, were used to stratify BCCs led to a working hierarchy of BCCs. The validity of the hierarchical BCCs was applied to blood samples from patients, during relapse, and before and after treatment. These studies resulted in the patients grouped with distinct BCCs in the circulation. The relevance of the latter findings are discussed with regards to prediction of treatment response and time of BC relapse. The findings require a larger cohort of patients in a prospective multi-center study. The stratification could be important to understand treatment response, strategies for alternative approaches, and an understanding of the interaction between particular BCC subsets and the tissue microenvironment.
Publication Title
Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci -- sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays.
Publication Title
A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b)
Description
GBM samples were clusered using gene expression of AKT pathway genes to reveal at least 5 GBM AKT subtypes, having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components.
Publication Title
AKT pathway genes define 5 prognostic subgroups in glioblastoma.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of this study was to identify differentially-expressed genes in CCR4hi/CXCR3- and CCR4lo CXCR3+ CCR6+ human Th17 cell subsets
Publication Title
Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of this study was to characterize the transcriptional signature of MDR1+ human memory T cells isolated from clinically inflamed gut tissue, and compare it to local MDR1- memory T cells
Publication Title
Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of this study was to identify differential gene expression resulting from the inhibition of RORgt in human CD4+ T cells.
Publication Title
Pharmacologic inhibition of RORγt regulates Th17 signature gene expression and suppresses cutaneous inflammation in vivo.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called Consensus Molecular Subtypes (CMS1-4), which each have a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the presence of CMSs in a large panel of CRC cell lines, primary cultures and patient-derived xenografts (PDX). We provide a repository encompassing this heterogeneity and moreover describe that a large part of the models can be robustly assigned to one of the four CMSs, independent of the stromal contribution. We subsequently validate our CMS stratification by functional analysis which for instance shows mesenchymal enrichment in CMS4 and metabolic dysregulation in CMS3. Finally, we observe a clear difference in sensitivity to chemotherapy-induced apoptosis, specifically between CMS2 and CMS4. This relates to the in vivo efficacy of chemotherapy, which delays outgrowth of CMS2, but not CMS4 xenografts. This indicates that molecular subtypes are faithfully modelled in the CRC cell cultures and PDXs, representing tumour cell intrinsic and stable features. This repository provides researchers with a platform to study CRC using the existing heterogeneity.
Publication Title
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples