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GSE18833
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Identification of genes that are involved in self-seeding by comparing gene expression profiles between parental MDA-MB-231 cells and seeder cells (MDA-231-S1a and S1b)
Publication Title
Tumor self-seeding by circulating cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Publication Title
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity. Overall design: We examined the transcriptional profile in control and RNaseH1 overexpression mouse ES cells during differentiation.
Publication Title
R loops regulate promoter-proximal chromatin architecture and cellular differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 42 Downloadable Samples
Description
TCF7L2 regulates multiple metabolic pathways in hepatocytes through a transcriptional network involving HNF4a Overall design: For the identification of Tcf7l2 target genes using a RNA-seq timecourse, and for identifying the binding sites of Tcf7l2 and Hnf4a, Tcf7l2 was silenced in rat H4IIE hepatocytes using siRNA for Tcf7l2 with a scrambled siRNA as control. Treatment times for RNA-seq samples were 3, 6, 9, 12, 15, 18, 48, and 96 hours, and for ChIP-seq samples 15 h. RNA-seq timecourse was performed in duplicate or triplicate, and the ChIP-seq in duplicate for Tcf7l2 and in singlicate for Hnf4a. The H4IIE-specific transcriptome was defined from an independent set of pooled 24 h siRNA treated samples (N=3 for siRNA for Tcf7l2 and N=3 for scrambled siRNA).
Publication Title
The mechanisms of genome-wide target gene regulation by TCF7L2 in liver cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 126 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Human cancers result from a complex series of genetic alterations resulting in heterogeneous disease states. Dissecting this heterogeneity is critical for understanding underlying mechanisms and providing opportunities for therapeutics matching the complexity. Mouse models of cancer have generally been employed to reduce this complexity and focus on the role of single genes. Nevertheless, our analysis of tumors arising in the MMTV-Myc model of mammary carcinogenesis reveals substantial heterogeneity, seen in both histological and expression phenotypes. One contribution to this heterogeneity is the substantial frequency of activating Ras mutations, the frequency of which can be changed by alterations in Myc. Additionally, we show that these Myc-induced mammary tumors exhibit even greater heterogeneity, revealed by distinct histological subtypes as well as distinct patterns of gene expression, than many other mouse models of tumorigenesis. Two of the major histological subtypes are characterized by differential patterns of cellular signaling pathways, including B-Catenin and Stat3 activities. We also demonstrate the predictive nature of this approach though examining metastatic potential. Together, these data reveal that a combination of histological and genomic analyses can uncover substantial heterogeneity in mammary tumor formation and therefore highlight aspects of tumor phenotype not evident in the population as a whole.
Publication Title
Genetic heterogeneity of Myc-induced mammary tumors reflecting diverse phenotypes including metastatic potential.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 141 Downloadable Samples
- NextSeq500
Description
Exploring the novel role of RORC (RORgamma) in breast cancer, utilizing NEXTseq with genetic gain and loss of function and pharmacological treatment. Overall design: For loss of function, control-siRNA or RORC-siRNA was transfected for 48h in three cell lines (MCF-7, T-47D and MDA-MB-231). For gain of function, CMV-empty or CMV-RORC was transfected for 48h in MDA-MB-231 cells. Furthermore, the selective RORC antagonist, SR2211 was utilized. MCF-7 cells were treated either DMSO or SR2211 (5uM) for 24h. Total RNA was extracted with the RNeasy kit. NEXTseq was performed for transcriptome analysis.
Publication Title
The Nuclear Receptor, RORγ, Regulates Pathways Necessary for Breast Cancer Metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of intestinal tuberculosis (ITB) and Crohn's disease (CD) in comparison to controls. Further, to evaluate the role of T regulatory cells, Foxp3 mRNA expression was quantified in serum as well as colonic biopsies of patients with intestinal tuberculosis, Crohn's disease and controls.
Publication Title
Genome-wide gene expression analysis for target genes to differentiate patients with intestinal tuberculosis and Crohn's disease and discriminative value of FOXP3 mRNA expression.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs).
Publication Title
Inhibitory role of Notch1 in calcific aortic valve disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated the clinical implications of lung developmental transcription factors (TTF-1, NKX2-8, and PAX9) which we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the three genes were determined and used to risk stratify a non-small cell lung cancer (NSCLC) clinical dataset consisting of ninety-one early stage tumors. Co-activation of the TTF-1 and NKX2-8 pathways identified a cluster of patients with poor survival, representing approximately 20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with co-activation of TTF-1 and NKX2-8 was validated in two other independent clinical datasets. Further, lung cancer cell lines showing co-activation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. Since TTF-1 and NKX2-8 lack specific inhibitors at the current time, we explored an alternative therapeutic strategy. Using signatures of signaling pathway activation, we identified deregulation of specific oncogenic pathways (Ras and Myc) in the TTF-1/NKX2-8 co-activated cohort.
Publication Title
Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study the function of 14-3-3, we established MCF-10A human mammary epithelial cells transduced with 14-3-3 (10A.) and vector (10A.Vec)
Publication Title
14-3-3ζ turns TGF-β's function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2.
Sample Metadata Fields
Specimen part, Cell line
View Samples