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GSE19564
Mus musculus
9 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Comparative analysis of Endodermal-like cell lines with demonstrated ability to support myocardial differentiation
Publication Title
A comparative analysis of extra-embryonic endoderm cell lines.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
IlluminaHiSeq2000
Description
FOXE3 is a lens specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, we have identified DNAJB1 as a transcriptional target of FOXE3 in a novel pathway that is crucial for development of the anterior segment of the eye. Overall design: Human Embryonic Kidney (HEK293FT) cells were transfected with the expression vector (pT-RexTM-DEST30) harboring either the wild type or the mutant (C240*) FOXE3 ORF (open reading frame). The experimental design included a total of eight biological replicates of cells expressing the wild type and eight replicates of mutant FOXE3 along with eight non-transfected controls. Cells were harvested 24-hour post-transfection and subjected to total RNA isolation for the preparation of whole transcriptome next-generation sequencing libraries. Initially, we examined the quality of transcriptome libraries on a MiSeq genome analyzer. Subsequent to confirmation of the quality, all libraries were paired-end sequenced (2 x 100 bp) using Illumina TruSeq Cluster V3 flow cell at a concentration of 13.0 pM in two separate lanes (12 bar-coded mRNA pooled libraries in each lane) on a HiSeq 2000 genome analyzer.
Publication Title
FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Students t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Students t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
Publication Title
The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism.
Publication Title
Distinct signature of altered homeostasis in aging rod photoreceptors: implications for retinal diseases.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study aims to define gene expression changes associated with mithramycin treatment of Ewing Sarcoma cell lines.
Publication Title
Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This dataset contains Affymetrix Mouse Genome 430 2.0 Array data obtained from K7M2 cells over-expressing ezrinT567A and the wild-type
Publication Title
Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development and thus aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. Indeed, knock-down of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell populations, thereby affecting erythroid differentiation. Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia.
Publication Title
The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 29 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans. However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis. Several lines of evidence supported this conclusion. First, both E9591 and LMT elicited a transcriptional response indicative of iron imbalance, causing the induction of genes that are required for iron uptake and for the maintenance of cellular iron homeostasis. Second, a genome-wide fitness profile analysis showed that yeast mutants with deletions in iron homeostasisrelated genes were hypersensitive to E9591 and LMT. Third, treatment of wild-type yeast cells with E9591 or LMT generated cellular defects that mimicked deficiencies in mitochondrial Fe-S cluster synthesis, including an increase in mitochondrial iron levels, a decrease in the activities of Fe-S cluster enzymes, a decrease in respiratory function, and an increase in oxidative stress. Collectively, our results demonstrate that E9591 and LMT perturb mitochondrial Fe-S cluster biosynthesis; thus, these two compounds target a cellular pathway that is distinct from the pathways commonly targeted by clinically used antifungal drugs. Therefore, the identification of this pathway as a target for antifungal compounds has potential applications in the development of new antifungal therapies.
Publication Title
Two plant-derived aporphinoid alkaloids exert their antifungal activity by disrupting mitochondrial iron-sulfur cluster biosynthesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. Aberrant hypermethylation in the promoter region of some known or putative tumor suppressor genes (TSGs) occurs frequently during the development of various cancers including head and neck squamous cell carcinoma (HNSCC). In this study we used an expanded mRNA expression profiling approach followed by microarray expression analysis to identify epigenetically inactivated genes in HNSCC. Two HNSCC cell lines were treated with 5-aza-2-deoxycytidine followed by microarray analysis to identify epigenetically silenced genes in HNSCC. 1960, 614, and 427 genes were upregulated in HNSCC cell lines JHU-012, JHU-011 and the combination of both cell lines, respectively. HNSCC tumor and normal mucosal samples were used for gene profiling by a 47K mRNA gene expression array and we found, 7140 genes were downregulated in HNSCC tumors compared to normal mucosa as determined by microarray analysis and were integrated with cell line data. Integrative analysis defined 126 candidate genes, of which only seven genes showed differentially methylation in tumors and no methylation in normal mucosa after bisulfite sequencing. After validation by QMSP, one gene, GNG7, was confirmed as being highly methylated in tumors and unmethylated in normal mucosal and salivary rinse samples demonstrating cancer-specific methylation in HNSCC tissues. TXNIP and TUSC2 were partially methylated in tumors and normal salivary rinses but unmethylated in normal mucosa. We concluded GNG7 as a highly specific promoter methylated gene associated with HNSCC. In addition, TXNIP and TUSC2 are also potential biomarkers for HNSCC.
Publication Title
Identification of guanine nucleotide-binding protein γ-7 as an epigenetically silenced gene in head and neck cancer by gene expression profiling.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study provides a comprehensive evaluation of changes in gene expression during treatment with Genistein in vitro.
Publication Title
Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.
Sample Metadata Fields
Treatment
View Samples