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SRP033699
Mus musculus
3 Downloadable Samples
Illumina HiSeq 2000
Description
Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in ESCs to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 mono-ubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1K3R3). We show that H2A.Z.1K3R3 is properly incorporated at target promoters in murine ESCs (mESCs), however, loss of mono-ubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and to faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member Brd2, are enriched in H2A.Z.1 chromatin. We further show that Brd2 is gained at de-repressed promoters in H2A.Z.1K3R3 mESCs whereas Brd2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and Brd2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs. Overall design: RNA-Seq analysis on mouse embryonic stem cells harboring H2A.Z or H2A.Z.K3R3 (3 C-terminal lysines mutated to arginines) tagged with YFP, in the presence of a knockdown hairpin targeting the endogenous H2A.Z transcript.
Publication Title
H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Chemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. The first aim of this study was to identify chemokines which are regulated during RV pressure overload. We then hypothesized that these chemokines regulate SLRPs (small leucine-rich proteoglycans)
Publication Title
Chemokines regulate small leucine-rich proteoglycans in the extracellular matrix of the pressure-overloaded right ventricle.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The effect of cafeteria (CAF) diet in PBMC gene expression was analyzed in two inbred rat strains
Publication Title
Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Mixed-lineage leukemias represent about 3-5% of acute leukemias occurring in patients of all ages and comprise several different subtypes (biphenotypic, bilineal, and lineage switch). The optimal therapeutic approach to these cases, especially in pediatric patients, has not been defined. We used microarrays to detail the gene expression of pediatric patients with biophenotypic leukemia.
Publication Title
Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Despite improved therapy, approximately one-fifth of children with acute T-lymphoblastic leukemia (T-ALL) succumb to the disease, suggesting unrecognized biologic heterogeneity that may contribute to drug resistance. We studied leukemic cells, collected at diagnosis, to identify features that could define this high-risk subgroup. A total of 139 patients with T-ALL were treated consecutively from 1992 to 2006 at this institution. Their leukemic cells were examined with multiparameter flow cytometry, single nucleotide polymorphism arrays and other methods of genomic analysis. Survival rates and probabilities of treatment failure were calculated for subgroups considered to have biologically distinct forms of T-ALL.
Publication Title
Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
In order to identify transcript changes in response to DEF , we used human macrophages with or without DEF treatment. In order to study the effect of iron chelation on LPS-polarized macrophage transcriptome, we exposed DEF-treated or control macrophages to short time exposure to LPS. We then performed whole-genome transcriptome sequencing by RNA-sequencing (RNA-seq). Overall design: Macrophages from 3 healthy donors were either treated with DEF (500 µM - designated as DEF) or left unstimulated (CONTROL). LPS treatment (100 ng/ml, 3 hours) was performed in cells with DEF (designated as LPS+DEF) or without (LPS). RNA-seq was performed on Illumina Hiseq 2500
Publication Title
Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The objective of this study was the assessment of transcriptional dysregulation in particular with regard to B-cell differentiation factors. Most studies focus on cross-section analyses of various leukemia subtypes to identify differentially regulated genes lacking suitable reference models. Here we applied comparative intraindividual transcriptome analysis of B-precursor ALL of childhood, which introduces a side-by-side analysis of leukemic cells and matched normal lymphoblasts from the same individual in complete continuous remission after the end of re-induction therapy. This approach reduces noise by eliminating interindividual variability.
Publication Title
Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
gamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray.
Publication Title
Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of the microarray experiment was to do a head-to-head comparison of the U1 Adaptor technology with siRNA in terms of specificity at the genome-wide level. U1 Adaptors represent a novel gene silencing method that employs a mechanism of action distinct from antisense and RNA interference (RNAi). The U1 Adaptor is a bifunctional oligonucleotide having a Target Domain that is complementary to a site in the target gene's terminal exon and a U1 Domain that binds to the U1 small nuclear RNA (snRNA) component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor. Tethering of U1 snRNP to the target pre-mRNA inhibits 3' end processing (i.e., polyA tail addition) leading to degradation of that RNA species within the nucleus thereby reducing mRNA levels. We demonstrate that U1 Adaptors can specifically inhibit both reporter and endogenous genes. Further, targeting the same gene either with multiple U1 Adaptors or with U1 Adaptors and small interfering RNAs (siRNAs), strongly enhances gene silencing, the latter as predicted from their distinct mechanisms of action. Such combinatorial targeting requires lower amounts of oligonucleotides to achieve potent silencing.
Publication Title
Gene silencing by synthetic U1 adaptors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into -cells. The induced -cells resemble islet -cells in morphology and histology, express genes essential for -cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
Publication Title
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples