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SRP060372
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2500
Description
Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. Overall design: mRNA profiles were generated by RNA-seq in duplicates for each of the following mESC lines: Foxd3fl/fl;Cre-ER mESC maintained in "Serum+LIF" (SL) treated with TM for three days (SL Foxd3-/-); untreated Foxd3fl/fl;Cre-ER SL mESC (SL Foxd3fl/fl); tetON Foxd3 SL mESC treated with Dox for three days; WT SL mESC treated with Dox for three days; Foxd3fl/fl;Cre-ER mESC maintained in "2i+LIF" (2i) treated with TM for three days (2i Foxd3-/-); untreated Foxd3fl/fl;Cre-ER 2i mESC (2i Foxd3fl/fl).
Publication Title
Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from mESC and AntNPC for the following lines: WT mESC, WT AntNPC, EED-/- mESC and EED-/- AntNPC
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from AntNPC derived from mESC: WT AntNPC (four biological replicates), PE Lhx5(-109)-/- Clon1 AntNPC (two biological replicates) and PE Lhx5(-109)-/- Clon2 AntNPC (two biological replicates).
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 45 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This data was used as an example to illustrate a computational method for assessing statistical significance in microarray experiments
Publication Title
Assessing statistical significance in microarray experiments using the distance between microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We propose a method to compare the location and variability of gene ex-pression between two groups of microarrays using a permutation test based on the pairwise distance between microarrays. The microarrays could be samples from distinct clinical or biological populations or microarrays prepared at two different levels of an experimental factor. For these tests the entire microarray or some pre-specifed subset of genes, not the individual gene, is the unit of analysis. We apply this method to compare results from two dfferent protocols for preparing labeled targets for microarray hybridization and their subsequent gene expression analysis.
Publication Title
Assessing statistical significance in microarray experiments using the distance between microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Publication Title
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Atrial identity is determined by a COUP-TFII regulatory network.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.
Publication Title
Atrial identity is determined by a COUP-TFII regulatory network.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.
Publication Title
A network-based analysis of systemic inflammation in humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 182 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma.
Publication Title
A genomic score prognostic of outcome in trauma patients.
Sample Metadata Fields
Sex, Age
View Samples