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SRP036145
Homo sapiens
3 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
We carried out a genome-wide investigation of the primary transcriptional targets of 1a,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1a,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1a,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1a,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1a,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1a,25(OH)2D3 treatment provides a resource of primary 1a,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaHiSeq2000
Description
investigation of lncRNAs deregulated in oncogenic induced senescence.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
The neuronal ceroid lipofuscinoses (NCL) are a group of childhood inherited neurodegenerative disorders characterized by blindness, early dementia and pronounced cortical atrophy. The similar pathological and clinical profiles of different forms of NCL suggest that common disease mechanisms may be involved. Here, we have performed quantitative gene expression profiling of cortex from targeted knock out mice produced for Cln1 and Cln5 to explore NCL-associated molecular pathways. Combined microarray datasets from both mouse models exposed a common affected pathway: genes regulating cytoskeletal dynamics and neuronal growth cone stabilization display similar aberrations. We analyzed locus specific gene expression and showed regional clustering of Cln1 and three major genes of this pathway, further supporting a close functional relationship between the corresponding gene products, Cap1, Ptprf and Ptp4a2. The evidence from the gene expression data was substantiated by immunohistochemical staining data of Cln1-/- and Cln5-/- cortical neurons. These primary neurons displayed abnormalities in beta-tubulin and actin as well as abnormal intracellular distribution of growth cone associated proteins GAP-43, synapsin and Rab3. Our data provide the first evidence for a common molecular pathogenesis behind neuronal degeneration in CLN1 and CLN5. Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCL.
Publication Title
Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Publication Title
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Saccharomyces cerevisiae
- 338 Downloadable Samples
- Illumina HiSeq 2500
Description
WT cells and mutants during growth on low phosphate levels and recovery
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Saccharomyces cerevisiae
- 200 Downloadable Samples
- Illumina HiSeq 2500
Description
WT and mutants cells during growth in low phosphate levels and recovery into 20mM phosphate
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Xenopus laevis
- 4 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Xenopus laevis embryos were injected with alpha-amanitin to inhibit RNA polymerase II activity. Embryos were allowed to develop up to stage 10.5 (early gastrula, control and alpha-amanitin injected embryos) and subsequently collected for RNA isolation. The transcriptome profiles of alpha-amanitin injected and control embryos were compared.
Publication Title
Robust activation of a Tbox-Gsc-Otx2 gene network independent of TATA binding protein family members
Sample Metadata Fields
Compound
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bronchial asthma is associated with type 2 immune responses induced by components of adaptive as well as innate immunity. Although innate cytokines such as IL-25 have been shown to play key roles in development of airway hyperreactivity (AHR), little is known of innate molecules that regulate IL-25-mediated airway inflammation. We found that blockade of repulsive guidance molecule b (RGMb) in an experimental murine model of asthma blocked the development of AHR, a cardinal feature of asthma, and that RGMb is expressed on F4/80+CD11b+CD11cneg macrophages (RGMb+ macrophages), which accumulated in the lungs of OVA-sensitized and challenged mice, but not in nave mice. Moreover, we found that a large fraction of the RGMb+ macrophages expressed the IL-25 receptor IL-17RB and produced IL-13. IL-25 was critical for the development of AHR in our model, since mice deficient in IL-17RB did not develop AHR. Finally, treatment with anti-RGMb mAb during the challenge phase of the protocol after allergen sensitization effectively prevented the development of AHR and airway inflammation, suggesting for the first time that RGMb+ cells, including RGMb+ macrophages, play critical roles in allergen-induced asthma.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The experiment was designed to generate a time series for epithelial model during development. Each time point had 3 replicates. The data set contained 5 time points over 10 days. They are day0, day3, day5,day7,day10.
Publication Title
Dynamic and physical clustering of gene expression during epidermal barrier formation in differentiating keratinocytes.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
It is currently debated as to whether liver macrophage (LM) activation from an anti-inflammatory to pro-inflammatory phenotype contributes to obesity-induced metabolic diseases. Here we report that LMs do not undergo a pro-inflammatory phenotype switch in obesity-induced insulin resistance in mice and humans. Remarkably, immune response related genes remained also unchanged in fly immune cells (haemocytes) upon high fat feeding. However, unbiased transcriptomic analyses revealed that LMs produce non-inflammatory factors, such as insulin like growth factor binding protein 7 (Igfbp7), that directly regulate liver metabolism. Using a unique method to manipulate gene expression only in LMs in vivo, we discovered that IGFBP7 specifically produced by LMs binds the insulin receptor and induces lipogenesis and gluconeogenesis, two major pathways increased in metabolic diseases. This study shows that macrophages could contribute to insulin resistance independently of their inflammatory status and that targeting non-inflammatory factors produced by macrophages might represent a better strategy than anti-inflammatory drugs to tackle metabolic diseases.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples