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Homo sapiens
8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA-binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44, and CTNND1 transcripts. To catalogue a larger set of splicing events under the regulation of the ESRPs, we profiled splicing changes induced by RNA interference-mediated knockdown of ESRP1 and ESRP2 expression in a human epithelial cell line using the splicing-sensitive Affymetrix Exon ST1.0 Arrays. Analysis of the microarray data using the previously described MADS tool resulted in the identification of over a hundred candidate ESRP-regulated splicing events. We were able to independently validate 37 of these targets by RT-PCR. The ESRP-regulated events encompass all known types of alternative splicing events. Importantly, a number of these regulated splicing events occur in gene transcripts that encode proteins with well-described roles in the regulation of actin cytoskeleton organization, cell-cell adhesion, cell polarity, and cell migration. In sum, this work reveals a novel list of transcripts differentially spliced in epithelial and mesenchymal cells, implying that coordinated alternative splicing plays a critical role in determination of cell type identity.
Publication Title
The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
IlluminaHiSeq2000
Description
The epithelial to mesenchymal transition (EMT) is an essential biological process during embryonic development and has also been implicated in cancer metastasis. Previous studies have characterized transcriptional regulation and key transcription factors that impact EMT. However, the role of alternative splicing (AS) regulation in EMT has only recently emerged and remains relatively uncharacterized. Here we used a robust in vitro EMT model to dynamically and comprehensively characterize splicing switches during EMT in a temporal manner. Overall design: We generated a H358 clone stably expressing a doxycycline (Dox)-inducible cDNA encoding a Zeb1-mCherry fusion protein. Over a 7-day time course following Dox treatment, cells have undergone EMT. We harvested total RNA and protein at each day of the EMT time course and a no Dox-treated control in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.
Publication Title
Determination of a Comprehensive Alternative Splicing Regulatory Network and Combinatorial Regulation by Key Factors during the Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genetically engineered mice developed spontaneous pancreas cancer (Pdx-Cre;LSL-KRASG12D;P53Mut). Mice were also engineered to develop similar spontaneous pancreas cancer without Twist or Snail (conditional gene knockout). The pancreas tumors were harvested and analysed for gene expression profiles comparisons.
Publication Title
Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Epithelial specific splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) are important regulators of alternative splicing during EMT. To study the alternative splicing events regulated by ESRP1/2 at a genome wide scale, we used lentiviral shRNAs to knockdown ESRP1/2 in H358 cells and performed RNA-seq in biological triplicates. Overall design: We used lentiviral based shRNAs targeting ESRP1 and ESRP2 to knockdown both regulators in human H358 cells. We harvested total RNA and protein from ESRP1/2 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.
Publication Title
Determination of a Comprehensive Alternative Splicing Regulatory Network and Combinatorial Regulation by Key Factors during the Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- NextSeq500, IlluminaGenomeAnalyzerIIx
Description
The MYC transcription factor is an unstable protein and its turnover is controlled by the ubiquitin system. Ubiquitination enhances MYC-dependent transactivation, but the underlying mechanism remains unresolved. Here we show that proteasomal turnover of MYC is dispensable for recruitment of RNA polymerase II (RNAPII), but is required to promote transcriptional elongation at MYC target genes. Degradation of MYC stimulates histone acetylation and recruitment of BRD4 and P-TEFb to target promoters, leading to phosphorylation of RNAPII CTD and the release of elongating RNAPII. In the absence of degradation, the RNA polymerase II-associated factor (PAF) complex associates with MYC via interaction of its CDC73 subunit with a conserved domain in the amino-terminus of MYC ("MYC box I"), suggesting that a MYC/PAF complex is an intermediate in transcriptional activation. Since histone acetylation depends on a second highly conserved domain in MYCs amino-terminus ("MYC box II"), we propose that both domains co-operate to transfer elongation factors onto paused RNAPII. Overall design: RNA-Seq Experiments were performed in a primary breast epithelial cell line (IMEC).The cell line expressed doxycycline-inducible versions of MYC (WT;Kless,Swap=WTN-KC). Where indicated cells were transfected with siRNAs (siCtrl;siSKP2). Where indicated cells were treaed with the proteasome inhibitor MG132 or EtOH as solvent control. DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control or comparing Dox-induced cells with EtOH (solvent control) treated cells.
Publication Title
Ubiquitin-Dependent Turnover of MYC Antagonizes MYC/PAF1C Complex Accumulation to Drive Transcriptional Elongation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Microarray studies was performed to analyze gene expression changes in NCI-H2347 cells after treatment with 50 M pioglitazone for 12hr, 24hr and 48hrs.
Publication Title
Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Zea mays
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Background: Maize plants developed typical gray leaf spot disease (GLS) symptoms initiating at the lower leaves and progressing to upper leaves through the season. Leaf material was collected at 77 days after planting, at which stage there were a large number of GLS disease necrotic lesions on lower leaves (8% surface area on average determined by digital image analysis), but very few lesions and only at chlorotic stage on leaves above the ear (average of 0.2% lesion surface area). Method:To collect material that reflected a difference between C.zeina infected B73 leaves and control B73 leaf material, samples were collected from two lower GLS infected leaves (second and third leaf internode below ear) , and two upper leaves with minimal GLS symptoms (second and third internode above ear), respectively. The two lower leaves from each plant were pooled prior to RNA extraction, and the two upper leaves from each plant were pooled prior to RNA extraction. Upper and lower leaf samples from three maize B73 plants were subjected to RNA sequencing individually. The three maize plants were selected randomly as one plant per row from three rows of ten B73 plants each. Result: A systems genetics strategy revealed regions on the maize genome underlying co-expression of genes in susceptible and resistance responses, including a set of 100 genes common to the susceptible response of sub-tropical and temperate maize. Overall design: To collect material that reflected a difference between C.zeina infected B73 leaves and control B73 leaf material, samples were collected from two lower GLS infected leaves (second and third leaf internode below ear) , and two upper leaves with minimal GLS symptoms (second and third internode above ear), respectively. The two lower leaves from each plant were pooled prior to RNA extraction, and the two upper leaves from each plant were pooled prior to RNA extraction. Upper and lower leaf samples from three maize B73 plants were subjected to RNA sequencing individually. The three maize plants were selected randomly as one plant per row from three rows of ten B73 plants each.
Publication Title
Systems genetics reveals a transcriptional network associated with susceptibility in the maize-grey leaf spot pathosystem.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Publication Title
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
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GSE1584- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse erythroid progenitors (EP) in comparison to granulocyte/monocyte - macrophage progenitors (GMP) from 10 - 16 week old C57/Bl6 - S129Ola (mixed genetic background) purified by flow cytometry
Publication Title
Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E).
Sample Metadata Fields
No sample metadata fields
View Samples