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GSE6890
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The three-dimensional (3D) folding of the chromosomal fibre in the human interphase nucleus is an important, but poorly understood aspect of gene regulation. Especially basic principles of 3D chromatin and chromosome organisation are still elusive. In this paper, we quantitatively analyse the 3D structure of large parts of chromosomes 1 and 11 in the G1 nucleus of human cells and relate it to the human transcriptome map (HTM). Despite a considerable cell-to-cell variation, our results show that subchromosomal domains, which are highly expressed, are more decondensed, have a more irregular shape and are located in the nuclear interior compared to clusters of low expressed genes. These aspects of chromosome structure are shared by six different cell lines and therefore are independent of cell type specific differences in gene expression within the investigated domains. Systematic measurements show that there is little to no intermingling of chromatin from different parts of the same chromosome, indicating that the chromosomal fibre itself is a compact structure. Together, our results reveal several basic aspects of 3D chromosome architecture, which are related to genome function.
Publication Title
The three-dimensional structure of human interphase chromosomes is related to the transcriptome map.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 43 Downloadable Samples
Illumina HiSeq 2500
Description
We studied gene expression by RNA-seq in yeast cells in various CDK1-cyclin-depleted states.
Publication Title
The CDK-APC/C Oscillator Predominantly Entrains Periodic Cell-Cycle Transcription.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts - an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. While the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness and anoikis-resistance. We find the E-cadherin binding partner beta-catenin to be necessary but not sufficient for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes.
Publication Title
Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs
Publication Title
Identification of selective inhibitors of cancer stem cells by high-throughput screening.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Through a loss-of-function approach, we identified that inhibition of the histone methyltransferase, Dot1L, accelerated somatic cell reprogramming, significantly increased the yield of induced pluripotent stem (iPS) cell colonies, and substituted for Klf4 and c-Myc in the reprogramming cocktail. To understand the mechanism by which Dot1L inhibition results in these phenotypes, we carried out gene expression profiling using Affymetrix microarrays.
Publication Title
Chromatin-modifying enzymes as modulators of reprogramming.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer protein that can specifically kill tumor cells while sparing healthy ones. Emerging evidences suggest that TRAIL resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at the epigenetic level is not understood. In this study, we aimed to identify novel epigenetic mechanisms regulating TRAIL response in Glioblastoma Multiforme (GBM) by a short-hairpin RNA (shRNA) screen. We employed an shRNA-mediated loss of function approach to interrogate the role of 48 genes in DNA and histone modification pathways. From this we identified KDM2B, an H3K36-specific demethylase, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity, the activation of Caspase-8, Caspase-3, Caspase-7, and cleavage of PARP. KDM2B knockdown also accelerated the apoptosis process, as revealed by live cell imaging experiments. Moreover, simultaneous knockdown of the methyltransferases responsible for generating the histone marks removed by KDM2B significantly recovered the cell death phenotype observed with KDM2B inhibition. To decipher the downstream molecular pathways regulated by KDM2B, levels of apoptosis-related genes were examined by RNA-sequencing and quantitative PCR upon KDM2B loss, which revealed de-repression of pro-apoptotic genes HRK, caspase-7, and DR4 and repression of anti-apoptotic gene Mcl-1. The apoptosis phenotype was dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. In vivo, KDM2B-silenced tumors exhibited slower growth and reduced angiogenic capacity compared to controls. Taken together, our findings suggest a novel mechanism regulating apoptotic response, where the key apoptosis components are under epigenetic control of KDM2B in GBM cells. Overall design: mRNA profiles of U87MG GBM cells transduced either by control shRNA or shRNA targeting KDM2B were generated by RNA-seq (Illumina HiSeq 2500). 2 biological replicates of shControl and shKDM2B total RNAs were barcoded individually and deep sequenced as 3 technical replicates each in 3 lanes.
Publication Title
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Microarrays were used to determine relative global gene expression changes upon introduction of EMT-inducing or control vectors.
Publication Title
Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiles of human embryonic stem cells, fibroblasts, and fibroblast-derived induced pluripotent stem cells
Publication Title
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
lincRNA-ST8SIA3 was depleted using siRNAs and associated gene expression changes were profiled on Affymentrix arrays
Publication Title
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples