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SRP140674
Caenorhabditis elegans
12 Downloadable Samples
Illumina HiSeq 4000
Description
How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A (BPA) in C. elegans. We show that BPA exposure causes the derepression of an epigenetically silenced transgene in the germline for 5 generations, regardless of ancestral response. ChIP-seq, histone modifications quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3 as well as with reproductive dysfunctions including germline apoptosis and embryonic lethality. Furthermore, targeting of the Jumonji demethylases JMJD-2 and JMJD-3/UTX-1 restores H3K9me3 and H3K27me3 levels, respectively, and fully alleviates the BPA-induced transgenerational effects. Together, our results demonstrate the central role of repressive histone modifications in the inheritance of reproductive defects elicited by a common environmental chemical exposure. Overall design: First generation C. elegans were exposed to either water, DMSO or BPA for for 48 hours, third generation (F3) worms were used for RNA-seq experiments.Total RNA was extracted from needle-dissected gonads of F3 adult worms in 4 replicates of H2O, DMSO, and BPA-exposed P0 nematodes.
Publication Title
The Memory of Environmental Chemical Exposure in C. elegans Is Dependent on the Jumonji Demethylases jmjd-2 and jmjd-3/utx-1.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Definitive hematopoietic cells arise from hemogenic endothelium during mid-gestation, indicating a direct link between blood and the endothelial-lined vessels. We sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here we demonstrate that transposon mutagenesis targeting endothelial cells in mice promotes the development of hematopoietic pathologies that are both myeloid and lymphoid in nature. Sequencing of the disrupted genes identified several previously recognized candidate cancer drivers and furthermore revealed that mutations in the lipid kinase Pi4ka can result in myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism that includes, but it is not limited to deregulation of Akt signaling. Finally, we provide evidence linking PI4KAP2, previously considered a “pseudogene”, with human myeloid and erythroid leukemia. Overall design: mRNA transcriptional comparison between two pieces of spleen from three SBxVEC-Cre+ animals and three control animals to assess clonality of each spleen as a whole.
Publication Title
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo an MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm. Overall design: Three independent clones for each genotype were generated. ZEB1+/+ and ZEB1+/- (generated using CRISPR-Cas9 gene editing) parental lines were initially generated, then transduced with lentivirus containing ZEB1 cDNA to generate ZEB1 transgenic lines of the parental lines.
Publication Title
ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyzed the global transcriptome signature over the time course of the cardiac differentiation from hESC by RNA-seq. We characterized the genome-wide transcriptome profile of 5 distinct stages; undifferentiated hESC (day 0), mesodermal precursor stage (hMP, day 2), cardiac progenitor stage (hCP, day 5), immature cardiomyocyte (hCM14) and hESC-CMS differentiated for 14 additional days (hCM28). While the stem cell signature decreases over the five stages, the signatures associated with heart and smooth muscle development increase, indicating the efficient cardiac differentiation of our protocol. Overall design: Five different temporal samples, two replicates for only first four samples day 0 through day 15
Publication Title
Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression profile for male SD Rats upon fructose treatment by RNA-Seq Overall design: male SD Rats were feed with fructose for 6 weeks
Publication Title
Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 14 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
Yeast lacking the H3 or H4 amino termini, and corresponding wild type strains, were grown in synthetic media. These conditions induce Gcn4-activated transcription.
Publication Title
Contribution of the histone H3 and H4 amino termini to Gcn4p- and Gcn5p-mediated transcription in yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Abf1 and Rap1 are General Regulatory Factors that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing, and telomere structure in yeast. In spite of their widespread roles in transcription, the scope of their functional targets genome-wide has not been previously determined. We have used microarrays to examine the contribution of these essential GRFs to transcription genome-wide, by using ts mutants that dissociate from their binding sites at 37 C. We combined this data with published ChIP-chip studies and motif analysis to identify probable direct targets for Abf1 and Rap1. We also identified a substantial number of genes likely to bind Rap1 or Abf1, but not affected by loss of GRF binding. Interestingly, the results strongly suggest that Rap1 can contribute to gene activation from farther upstream than can Abf1. Also, consistent with previous work, more genes that bind Abf1 are unaffected by loss of binding than those that bind Rap1. Finally, we showed for several such genes that the Abf1 C-terminal region, which contains the putative activation domain, is not needed to confer this peculiar "memory effect" that allows continued transcription after loss of Abf1 binding.
Publication Title
Genome-wide analysis of transcriptional dependence and probable target sites for Abf1 and Rap1 in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Signal intensity data for rpd3 delete, H3delta(1-28), H3(K4,9,14,18,23,27Q), H4delta(2-26), H4(K5,8,12,16Q), rpd3 delete H3delta(1-28), and rpd3 delete H4(K5,8,12,16Q) yeast grown in rich (YPD) media
Publication Title
Genome-wide analysis of the relationship between transcriptional regulation by Rpd3p and the histone H3 and H4 amino termini in budding yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Differential gene expression between groups of homogenous cell types is a biological question whose time has come. RNA can be extracted from small numbers of cells, such as those isolated by laser capture microdissection, but the small amounts obtained often require amplification to enable whole genome transcriptome profiling by technologies such as microarray analysis and RNA-seq. Recently, advances in amplification procedures make amplification directly from whole cell lysates possible. The aim of this study was to compare two amplification systems for variations in observed RNA abundance attributable to the amplification procedure for use with small quantities of cells isolated by laser capture microdissection. Arabidopsis root cells undergoing giant cell formation due to nematode infestation and un-infested control root cells were laser captured and used to evaluate 2 amplification systems. One, NuGEN's WT-Ovation Pico amplification system, uses total RNA as starting material while the other, NuGEN's WT-One-Direct Amplification system, uses lysate containing the captured cells. The reproducibility of whole genome transcript profiling and correlations of both systems were investigated after microarray analysis. The NuGEN WT-Ovation One-Direct system was less reproducible and more variable than the NuGEN WT-Ovation Pico system. The NuGEN WT-Ovation Pico Amplification kit resulted in the detection of thousands of genes differentially expressed genes between giant cells and control cells. This is in marked contrast to the relatively few genes detected after amplification with the NuGEN WT-Ovation One-Direct Amplification kit.
Publication Title
Comparison between NuGEN's WT-Ovation Pico and one-direct amplification systems.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Conditional IRF8 KO mice (mice with a conditional allele of Irf8 crossed with CD19-Cre mice) showed increased numbers of both Gene expression data spleen marginal zone (MZ) and Gene expression data spleen follicular (FO) B cells compared to control mice.
Publication Title
IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
Sample Metadata Fields
No sample metadata fields
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