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GSE40828
Homo sapiens
15 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
We have developed cdk4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) to study lung cancer pathogenesis. By studying the oncogenic effect of common lung cancer alterations (p53, KRAS, and c-MYC) we demonstrate the ability of this model to characterize the stepwise transformation of bronchial epithelial cells to full malignancy. Using HBECs derived from multiple individuals we found: 1) the combination of five genetic alterations (p53, KRASV12, c-MYC, CDK4 and hTERT) is sufficient for full tumorigenic conversion of HBECs; 2) high levels of KRASV12 are required for full malignant transformation of HBECs, however these levels also stimulate oncogene-induced senescence; 3) RAS-induced senescence is largely bypassed with loss of p53 function; 4) over-expression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; 5) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; 6) serum-induced epithelial-to-mesenchymal transition (EMT) increases in vivo tumorigenicity; 7) genetically-identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation as well as sensitivity to standard platinum-based chemotherapies; and 8) an mRNA signature derived from tumorigenic and non-tumorigenic clones is predictive of outcome in lung cancer patients. Collectively, we demonstrate this HBEC model system can be used to study the effect of oncogenic mutations on malignant progression, oncogene-induced senescence, and EMT along with clinically translatable applications such as development of prognostic signatures and drug response phenotypes.
Publication Title
Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
KRAS mutations occur in approximately 25% of non-small cell lung cancer (NSCLC). They account for the therapy resistance to EGFR inhibitors and are suggested to be difficult to target by specific drugs. Therefore, new therapies for KRAS mutant NSCLC are urgently needed. The histone H3K4 and H3K9 di/mono-demethylase KDM1A is a key epigenetic writer, aberrantly upregulated in many cancer types, including NSCLC. In order to understand the functional role of KDM1A in the progression of lung adenocarcinoma, KDM1A expression profiles were analysed in tissue microarrays (TMAs) including 182 lung adenocarcinoma. KDM1A expression correlated with high grade and metastasized tumor. To investigate the impact of KDM1A in lung adenocarcinoma development, we used the KRAS mutated A549 cell line to establish a shRNA-mediated stable KDM1A knockdown cell clone. Unexpectedly, KDM1A knockdown had only a slight effect on retardation of cell growth. However, cell invasion and self-renewal capability was significantly decreased by KDM1A inhibition. KDM1A knockdown in A549 cell resulted in a dramatic change in the transcriptome profile as determined by RNA-Seq. Interestingly, genes involved in the KRAS signature and lung epithelial marker genes were significantly affected upon KDM1A knockdown. Ingenuity pathway analysis also suggested that the alternative integrin ß3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin ß3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-?B activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin ß3 level was validated in TMAs. Overall design: Determining the role of KDM1A in A549 cells, mRNA profiles of control and knockdown samples of A549 cells, generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
Publication Title
LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Sequencing of 5'' ends of RNA molecules from control and exosome-depleted S2 cells. Overall design: CAGE library construction from RNA extracted from control and exosome-depleted cells.
Publication Title
Transcription start site analysis reveals widespread divergent transcription in D. melanogaster and core promoter-encoded enhancer activities.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Characterization of gene expression changes upon development of taxane-platin drug resistance in NSCLC cells and further, upon treatment of these resistant cells with the Jumonji KDM inhibitor, GSK-J4. Overall design: Comparison of gene expression changes between H1299 Parental cells (chemo-sensitive) and H1299 T18 cells (taxane-platin resistant), and comparison of H1299 T18: GSK-J4 treated vs. H1299 T18: DMSO control.
Publication Title
Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors.
Sample Metadata Fields
Sex, Age, Treatment, Race, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). While the mechanisms that lead to vascular permeability are unknown, the endothelium plays a central role in regulating fluid and cellular efflux from capillaries. Thus, dysregulation of endothelial cells functions by dengue virus infection may contribute to pathogenesis and severe disease.
Publication Title
Endothelial cells elicit immune-enhancing responses to dengue virus infection.
Sample Metadata Fields
Specimen part, Time
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We report RNA-seq data obtained from FACS-isolated live neurons at third instar larval or P14 pupal stage, and from BG3 cells. RNA from neurons with RNAi-based loss of shep or GFP control is used to construct stranded RNA-seq library. RNA from BG3 cells treated with dsRNA targeting shep or GFP is used to construct RNA-seq library. Overall design: RNA-seq data of loss-of-shep neurons and control neurons in larval and pupal stages, and from shep-depleted or control BG3 cells.
Publication Title
Shep regulates <i>Drosophila</i> neuronal remodeling by controlling transcription of its chromatin targets.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
- Illumina Genome Analyzer II, Illumina HiSeq 2000
Description
Chromatin insulators are DNA-protein complexes situated throughout the genome capable of demarcating independent transcriptional domains. Previous studies point to an important role for RNA in gypsy chromatin insulator function in Drosophila; however, the identity of these putative insulator-associated RNAs is not currently known. Here we utilize RNA-immunoprecipitation and high throughput sequencing (RIP-seq) to isolate RNAs stably associated with gypsy insulator complexes. Strikingly, these RNAs correspond to specific sense-strand, spliced, and polyadenylated mRNAs, including two insulator protein transcripts. In order to assess the functional significance of these associated mRNAs independent of their coding function, we expressed untranslatable versions of these transcripts in developing flies and observed both alteration of insulator complex nuclear localization as well as improvement of enhancer-blocking activity. Together these data suggest a novel, noncoding mechanism by which certain mRNAs contribute to chromatin insulator function. Overall design: RIP-seq of insulator proteins with different library preparations and multiple biological replicates
Publication Title
Messenger RNA is a functional component of a chromatin insulator complex.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human iPS cells derived from normal and Fragile-X fibroblasts in order to assess the capability of Fragile-X iPS cells to be used as a model for different aspects of Fragile-X syndrome. Microarry analysis used to compare global gene expression between human ES cells, the normal and the mutant iPS cells and the original fibroblasts, to demonstrate that the overall reprogramming process succeeded, and that the FX-iPS cells are fully reprogrammed cells.
Publication Title
Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Overall design: Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
Publication Title
Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Carbonic anhydrase 1 (Car1), an early specific marker of the erythroid differentiation, has been used to distinguish fetal and adult erythroid cells since its production closely follows the - to -globin transition, but the molecular mechanism underlying transcriptional regulation of Car1 is unclear. Here, we show that Car1 mRNA decreases significantly when erythroid differentiation is induced in MEL cells. The Ldb1 protein complex including GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced enrichment of the complex during differentiation correlates with loss of Car1 expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for recruitment of Pol II as well as the transcription regulator P-TEFb to enhance elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a regulatory complex to maintain Car1 expression in erythroid cells.
Publication Title
Ldb1 regulates carbonic anhydrase 1 during erythroid differentiation.
Sample Metadata Fields
Specimen part
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