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SRP049208
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
The chromatin modifying enzymes that drive the erythroid-specific transcription program are incompletely understood. Setd8 is the sole histone methyltransferase in mammals capable of generating mono-methylated histone H4 lysine 20 (H4K20me1) and is expressed at significantly higher levels in erythroid cells than any other cell- or tissue- type, suggesting that Setd8 has an erythroid-specific function. To test this hypothesis, stable knockdown of Setd8 was established in extensively self-renewing erythroblasts (ESREs), a well-characterized, non-transformed, model of erythroid maturation. Setd8 knockdown impaired erythroid maturation, characterized by a delay in hemoglobin accumulation, larger cell area, persistent kit expression, incomplete nuclear condensation, and lower rates of enucleation than control cells. Setd8 knockdown did not alter ESRE proliferation or viability, or result in accumulation of DNA damage. Global gene expression analyses following Setd8 knockdown suggests that in erythroid cells, Setd8 functions primarily as a repressor and demonstrated high levels of Gata2 expression. Setd8 occupies critical regulatory elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1 and gain of H4 acetylation at the Gata2 1S promoter. Taken together, these results imply that Setd8 is an important regulator of erythroid maturation that works in part through repression of Gata2. Overall design: RNA-seq was performed of Setd8 knockdown and control cells, both while the cells were proliferating, and after 6 hours of maturation.
Publication Title
Histone methyltransferase Setd8 represses Gata2 expression and regulates erythroid maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
Publication Title
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons
Publication Title
Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines and increased production of interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS (169 in only the young, 184 in only the aged, and 500 in both). Expression analysis of systematic explorer revealed that immune response (proinflammatory chemokines, cytokines, and their receptors) and signal transduction genes were specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6 was reduced, and Il10 was increased, confirming our previous results. There was also decreased expression of interferon-gamma. Genes in the Toll-like receptor-signaling pathway leading to nuclear factor-kappaB activation were also down-regulated but IL-1 receptor-associated kinase 3, a negative regulator of this pathway, was increased in aged mice. An increase in expression of the gene for p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding increase in protein expression and enzyme activity confirmed by Western blotting. Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK activity has a role in cytokine dysregulation in the aged mouse Mphi.
Publication Title
Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray analysis of gene expression in the olfactory epithelium of macrophage depleted mice to study the role of macrophages in regulating neurodegeneration, neuroprotection, and neurogenesis of olfactory sensory neurons
Publication Title
Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
CTCF is an organizer of higher-order chromatin structure, and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, there is no knowledge of the role of CTCF-mediated chromatin structure in learning and memory. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization. Cognitive disabilities are associated with downregulation of cadherin and learning-related genes. In addition, CTCF knockdown attenuates fear conditioning-induced hippocampal gene expression of key learning genes and loss of long-range interactions at the BDNF and Arc loci. This study identifies CTCF-dependent gene expression regulation and DNA structure as regulators of learning and memory. Overall design: 3 biological replicates of wild type and 3 biological replicates of CTCF cko mice
Publication Title
Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Skin squamous cell carcinomas are among the most frequent human cancers. In this study we compared the expression profiles of 10 skin SCCs with a set of 3 normal human epidermis controls.
Publication Title
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of human peripheral blood T cells
Publication Title
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of human peripheral blood monocytes
Publication Title
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 259 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To evaluate the transcriptomes of lesional skin from different body parts of the same individual. Specifically, we conducted a transcriptomic study to investigate expression variability for diseased samples taken from different anatomic regions of same patient, and to compare the variability to between individuals variability. Overall design: 5 psoriasis patients, each with 4 psoriatic and 1 uninvolved skin biopsies. Totally 25 RNA-seq experiments conducted.
Publication Title
Transcriptional determinants of individualized inflammatory responses at anatomically separate sites.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples