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SRP119158
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
MicroRNAs inhibit gene expression by recruiting the RNA-induced silencing complex (RISC) to mRNAs in a process termed RNA interference (RNAi). While it is generally accepted that RNAi modulates gene expression pervasively, the number of mRNAs bound and repressed by miRNAs in vivo in individual cell types remains unknown, with estimates ranging from a few hundred genes to many thousands. We examined microRNA activities in primary cells by combining genetic loss of function with RNA-sequencing, quantitative proteomics and High-Throughput Sequencing of RNA isolated by Crosslinking Immunoprecipitation (HITS-CLIP), focusing on miR-144/451, the most highly expressed microRNA locus during red blood cell (RBC) formation. We show that Argonaute (Ago) protein binds over one thousand different mRNAs in a miR-144/451-dependent manner, accounting for one third of all Ago-bound mRNAs. However, only about 100 mRNAs are stabilized in RBC precursors after ablation of the miR-144/451 locus. Thus, Ago-miRNA complexes destabilize only a small subset of bound mRNAs, probably no more than a few hundred in erythroblasts under physiological conditions. Our integrated approach identified more than 50 new miR-144/451 target mRNAs, including Cox10, which facilitates assembly of the mitochondrial cytochrome c oxidase (COX) electron transport complex. Loss of miR-144/451 resulted in increased Cox10 expression, accumulation of the COX complex, and increased mitochondrial membrane potential with no change in mitochondrial mass. Thus, miR-144/451 represses mitochondrial respiration during erythropoiesis by inhibiting Cox10. Overall design: HITS-CLIP analysis of 3 WT mice fetal livers vs 3 miR-144/451 KO mice fetal livers
Publication Title
Regulation of gene expression by miR-144/451 during mouse erythropoiesis.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Here, we examined the role of intestinal epithelial specific tumor suppressive function of 53. We provide evidence that p53 plays a dual role during carcinogen-induced tumorigenesis. At the initiation stage, p53 controls DNA damage and survival of initiated epithelia. In contrast, at later stages, loss of p53 is associated with the formation of an inflammatory microenvironment that is linked to epithelial mesenchymal transition, invasion and metastasis and the activation of NF-kappaB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function during the progression stage of colorectal cancer that is independent of its well-established role in cell cycle regulation, apoptosis and senescence.
Publication Title
Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 342 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Normal human tissue samples from ten post-mortem donors were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. Donor information: Donor 1 - 25 year old male; donor 2 - 38 year old male; donor 3 - 39 year old female; donor 4 - 30 year old male; donor 5 - 35 year old male; donor 6 - 52 year old male; donor 7 - 50 year old female; donor 8 - 48 year old female; donor 9 - 53 year old female; donor 10 - 23 year old female
Publication Title
Gene expression analyses reveal molecular relationships among 20 regions of the human CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 73 Downloadable Samples
- Illumina HiSeq 2500
Description
Using fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after pneumonectomy procedure. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Using the pneumonectomy dataset, we identified 6 cell groups and 4 gene groups that marked several regenerative macrophage subsets including CCR2+, Ly6C+ monocytes and CD206+, Chil3+ M2-like macrophages. Overall design: individual macrophages 7 days post-pneumonectomy in a B6 CSF1R-GFP mouse
Publication Title
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Using fluorescence activated cell sorting, we isolated CD45+, CSF1R-GFP+, F4/80+, Ly6G- mouse lung monocytes and macrophages at 7 days after sham thoracotomy procedures. We then used microfluidic single cell RNA-sequencing to transcriptional profile unique myeloid subsets. Overall design: After sequencing 31 single cell transcriptomes were analyzed. Hierarcical and k-means clustering reveals several populations of macrophages are present in the lung.
Publication Title
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 280 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Gene expression profiles from 280 formalin-fixed and paraffin embedded normal and tumor samples of four cancer types
Publication Title
Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Cystic Fibrosis lung disease progresses by a combination of accelerated airways inflammation and bacterial colonization and infection. Airways inflammation in CF is predominantly neutrophilic and complicates airway clearance therapies through cellular debris, excessive DNA, excessive and viscous mucous, and high concentrations of neutrophils,Il-8 and related cytokines liberated along the NFkB signaling pathway. We conducted a single site, randomized, double blind, placebo-controlled, proof-of-concept trial in which we evaluated the effects of 28 days of two dose levels (0.05 mg and 0.10 mg daily) of an older cardiac glycoside, digitoxin, as compared with placebo, on inflammatory markers in induced sputum obtained from 24 subjects with mild to moderate CF lung disease. Nasal epithelial cells from 23 subjects were analyzed for microarray analysis. CF patients 18 to 45 years old, any genotype combination, were eligible.
Publication Title
Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Staphylococcus aureus
- 12 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Treatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully 13C-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 minutes and 3 hours after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful towards the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology.
Publication Title
Metabolic and transcriptional activities of Staphylococcus aureus challenged with high-doses of daptomycin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Background and Aims: Analysis of aging-induced impairments in satellite cells (SCs) – the stem cells of skeletal muscle that are required for its regeneration. Hox genes are known to control stem cell function and development of various tissues. Overall design: Hindlimb muscles from young adult (3-4 months) and old (22-28 months) C57BL/6J mice were injured by BaCl2 injection in order to induce satellite cell activation. Satellite cells were isolated 3 days after injury and gene expression was analyzed.
Publication Title
Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Macaca mulatta
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
Publication Title
Gene expression in primate liver during viral hemorrhagic fever.
Sample Metadata Fields
Specimen part, Time
View Samples