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SRP069300
Drosophila melanogaster
12 Downloadable Samples
Illumina HiSeq 2000
Description
Pulsed ecdysone signaling remodels cell cycle dynamics, causing distinct primary and secondary cell cycle arrests, similar to those observed in the wing during metamorphosis. Overall design: This was a timecourse transcriptome analysis of the Drosophila pupal wing during metamorphosis by RNAseq. Timepoints include the proliferative wandering L3 larval stage (-10h APF), the temporary G2 arrest (6h APF) the final cell cycle (18h APF) the permanent cell cycle arrest (24h APF), and stages of terminal differentiation including vein differentiation, wing hair formation and cuticle protein production (36 and 44h APF)
Publication Title
Chromatin organization changes during the establishment and maintenance of the postmitotic state.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
FOXC1 is a critical marker for basal-like breast cancer. To explore the role of FOXC1 in regulation of basal-like breast cancer cell function, we performed microarray assays and discovered that some known cancer-related genes were regulated by FOXC1.
Publication Title
FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human dendritic cells (DC) are suppressed by tumor-derived alpha fetoprotein (AFP), but less so by cord blood-derived normal AFP.
Publication Title
Tumor-derived α-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 111 Downloadable Samples
- Illumina HiSeq 2000
Description
Alternative splicing and mRNA editing are known to contribute to transcriptome diversity. Although alternative splicing is pervasive and known to contribute to a variety of pathologies, including cancer, the genetic context for individual differences in isoform usage is still evolving. Similarly, although mRNA editing is ubiquitous and associated with important biological processes such as intracellular viral replication and cancer development, individual variations in and the genetic transmissibility of mRNA editing are equivocal. Here, we have used linkage analysis to show that both mRNA editing and alternative splicing are regulated by the macrophage genetic background and environmental cues. We show that distinct loci, potentially harboring variable splice factors, regulate the splicing of multiple transcripts. Additionally, we show that individual genetic variability at the Apobec1 locus results in differential rates of C-to-U(T) editing in murine macrophages; with mouse strains expressing mostly a truncated isoform of Apobec1 exhibiting lower rates of editing. As a proof of concept, we have used linkage analysis to identify 36 high confidence novel edited sites. These results provide a novel and complementary method that can be used to identify C-to-U editing sites in individuals segregating at specific loci and show that, beyond individual DNA sequence and structural changes, differential isoform usage and mRNA editing can contribute to intra-species genomic and phenotypic diversity. Overall design: Bone marrow derived macrophages (BMDM) from female AxB/BxA mice were left unstimulated or stimulated with IFNG/TNF, or CpG for 18 hrs or infected with infected with type II (Pru A7) for 8 hrs. The transcriptional response was then measured using the illumina RNA-seq protocol on an illumuna HiSeq 2000.
Publication Title
The genetic basis for individual differences in mRNA splicing and APOBEC1 editing activity in murine macrophages.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Overall design: Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for RNA-seq.
Publication Title
Polycomb Repressive Complex 2 regulates lineage fidelity during embryonic stem cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
Objectives: The collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies, but the pathogenesis, including the role of mutant collagen VI in the matrix is poorly understood. To better define the pathways disrupted by mutations in collagen VI, we have used a transcriptional profiling approach with RNA-Seq to identify differentially expressed genes in COL6-RD patients from controls. Methods: We have used RNA-Seq to identify differentially expressed genes in cultured dermal fibroblasts from 13 COL6-RD patients (8 dominant negative and 5 null) and 6 controls. Sequence reads were analyzed using the TopHat/Cufflinks pipeline. Results: Differentially expressed transcripts between COL6-RD patient and control fibroblasts include upregulation of ECM components and downregulation of factors controlling matrix remodeling and repair. DN and null samples are differentiated by downregulation of genes involved with DNA replication and repair in null samples Overall design: Expression profiles of dermal fibroblasts from 13 COL6-RD patients with dominant negative (8) or null (5) mutations compared to 6 control fibroblasts.
Publication Title
Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 17 Downloadable Samples
- NextSeq 500
Description
RNA-seq of Wild Type (N2), pmk-1 or atf-7 mutant animals exposed to either non-pathogenic E. coli OP50 or pathogenic P. aeruginosa PA14 Overall design: mRNA profiles were generated using 3 replicates (>1,000 animals each) of each condition were prepared and sequenced, except for atf-7(qd22qd130) on PA14 which had only 2 replicates. Sequenced on Illumina NextSeq 500
Publication Title
Global transcriptional regulation of innate immunity by ATF-7 in C. elegans.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Publication Title
Characterization of genetic loss-of-function of Fus in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Therapy-induced developmental reprogramming of prostate cancer cells and acquired therapy resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Hepatocellular carcinoma (HCC) is a fatal malignancy with a dismal prognosis. The recent advances in genomics and transcriptomics have led to large volumes of molecular data for HCC, providing an unprecedented opportunity to translate these data into more effective therapeutics. By creating HCC gene expression signatures and comparing with drug response signatures from multiple datasets, we identified four antihelminthics (from over 1000 FDA-approved drugs) that can reverse the HCC disease gene expression. Among these four, niclosamide was the top hit, which we further evaluated in clinically relevant HCC cell lines and patient-derived xenografts (PDX). Given the poor water-solubility and limited systemic bioavailability of niclosamide, we also evaluated its ethanolamine salt (NEN), which has improved solubility and bioavailability. Both niclosamide and NEN significantly inhibited HCC cell proliferation in vitro, which was associated with down-regulation of key proteins involved in the AKT-mTOR, Wnt, Stat3, and EGFR/Ras/Raf signaling pathways. NEN additionally decreased the growth of three PDX models after oral administration (1,5000 ppm in food) for 4-6 weeks. Expression profiling demonstrated that niclosamide and NEN induced highly similar gene expression changes in HepG2 cells and in PDX models, and that both compounds significantly reversed HCC gene expression in vitro and in vivo . Our results suggest that NEN may be a preferred drug candidate for the treatment of HCC.
Publication Title
Computational Discovery of Niclosamide Ethanolamine, a Repurposed Drug Candidate That Reduces Growth of Hepatocellular Carcinoma Cells In Vitro and in Mice by Inhibiting Cell Division Cycle 37 Signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples