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SRP149588
Drosophila melanogaster
15 Downloadable Samples
NextSeq 500
Description
The spliceosome is a dynamic RNA-protein complex that executes pre-mRNA splicing and is composed of five core small nuclear ribonucleoprotein particles (U1, U2, U4/5/6 snRNP) and >150 additional proteins specific for each snRNP. We report a circadian role for Pre-mRNA Processing factor 4 (PRP4), a conserved component of the spliceosomal U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) complex. We broadly hypothesized that downregulation of prp4 led to the aberrant splicing of one or many of the core clock transcripts. To identify these splicing events in an unbiased way, we performed RNA-Sequencing (RNA-Seq) analysis. We reasoned that we could have a more targeted approach if we could zoom in on the overlapping splicing changes that would be driven by the knockdown of at least two different tri-snRNP components. Because the pan-neuronal knockdown of all tri-snRNP components tested in our study led to lethality, we decided to utilize an alternative broad driver. For that purpose, we selected a strong eye-specific Glass Multiple Promoter driver (GMR-Gal4). Because most of the signal from head lysates comes directly from the eye tissue and because the core splicing factors are ubiquitously expressed, GMR-specific downregulation of prp4 and prp8 promised to be a viable alternative to the pan-neuronal knockdown. We examined changes in both the total transcript levels and splicing events upon prp4 knockdown in the eye. The overall gene expression seemed to be dramatically influenced by prp4 downregulation (433 DOWN, 310 UP at FDR < 0.05). Despite the fact that PRP4 is a component of the core spliceosome that is required for constitutive exon splicing, we did not detect dramatic effects on global splicing. Only 45 genes exhibited differential alternate splicing upon prp4 downregulation at FDR < 0.05). Overall design: 3 samples with 5 replicates each were analyzed using Illumina Next-Generation Sequencing (NextSeq 500).
Publication Title
Spliceosome factors target timeless (<i>tim</i>) mRNA to control clock protein accumulation and circadian behavior in Drosophila.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 285 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to examine gene expression levels from 95 unrelated CEPH-Utah individuals 0, 2 or 6 hours after treatment with 10Gy of ionizing radiation.
Publication Title
Stress-induced changes in gene interactions in human cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 258 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to examine gene expression levels from 131 unrelated CEPH-Utah grandparents with either DMSO or tunicamycin.
Publication Title
Stress-induced changes in gene interactions in human cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 220 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in the condition called ER stress which induces the unfolded protein response (UPR) which is a complex cellular process that includes changes in expression of many genes. Failure to restore homeostasis in the ER is associated with human diseases. To identify the underlying changes in gene expression in response to ER stress, we induced ER stress in human B-cells and then measured gene expression at 10 time-points. We followed up those results by studying cells from 60 unrelated people. We rediscovered genes that were known to play a role in ER stress response and uncovered several thousand genes that are not known to be involved. Two of these are VLDLR and INHBE which showed significant increase in expression following ER stress in B-cells and
Publication Title
Gene expression and genetic variation in response to endoplasmic reticulum stress in human cells.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Stem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies.
Publication Title
Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We have determined that verticillin A is a histone methyltransfease inhibitor that selectively inhibits human SUV39H1, SUV39H2, G9a and GLP to inhibit H3K9 methylation in human colon cancer cells. The objective here is to identify verticillin A target genes in human colon cancer cells.
Publication Title
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Regulation of homeostasis and development of cardiac muscle tissues is controlled by a core set of transcription factors. The MEF2 family plays a critical role in these processes.
Publication Title
Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study, we have identified MEF2A-sensitive genes in atrial and ventricular chambers of the adult heart. MEF2A is a member of the myocyte enhancer factor 2 (MEF2) family of transcription factors. MEF2 proteins are expressed in skeletal and cardiac muscle tissues and are conserved across many mammalian species, but the gene programs regulated by MEF2A in adult cardiac chambers are largely unknown. We compared gene expression profiles between WT and Mef2a knockout atria and ventricles from adult mice, and the results identified distinct and overlapping sets of genes sensitive to the loss of MEF2A in the adult heart.
Publication Title
The transcription factor MEF2A fine-tunes gene expression in the atrial and ventricular chambers of the adult heart.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Publication Title
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2500
Description
Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/ß-catenin response for scheduled regression. Transcriptome analysis of the postnatal day 5 mouse hyaloid showed expression of several Wnt pathway proteins. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc, and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/ß-catenin signaling in hyaloid vascular endothelial cells (VECs). We also showed that both Myc and Cdkn1a are downstream of the Wnt response and are required for hyaloid regression but for different reasons. Conditional deletion of Myc in VECs suppressed both proliferation and cell death. By contrast, conditional deletion of Cdkn1a resulted in VEC over-proliferation that countered the effects of cell death on regression. When combined with analysis of MYC, and P21 protein levels, this analysis suggests that a Wnt/ß-catenin, MYC-P21 pathway regulates scheduled hyaloid vessel regression. Overall design: Hyaloid vascular preparations from postnatal day 5 mice were harvested in cold PBS and RNA extracted in Tri Reagent. RNA amplifcation was performed on total RNA before cDNA library was made. Samples were then sequenced using Illimina HiSeq2500 to obtain 25-30 million paired-end reads.
Publication Title
Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death.
Sample Metadata Fields
Specimen part, Subject
View Samples