This SuperSeries is composed of the SubSeries listed below.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesTranscriptomic comparison of 5 cell types during lethal and non-lethal influenza infection and further use of these signatures in a top-down systems analysis investigating the relative pathogenic contributions of direct viral damage to lung epithelium vs. dysregulated immunity during lethal influenza infection.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesDendritic cells (DC) are the most potent antigen-presenting cells of the immune system. In lymph nodes (LN), they are also believed to dispose of apoptotic cells, a critical function usually achieved by macrophages (M) in other tissues. We report a population of tolerogenic M located in the T cell zone of LN. T zone M (TZM) are long lived M seeded after birth and slowly replaced by blood monocytes. We show that TZM but not DC act as the only professional scavengers clearing apoptotic cells in the LN T cell zone. Importantly, we demonstrate that TZM prevent the capture of apoptotic cells by DC and the associated potential noxious activation of T cell immunity. We thus propose a new model in which efferocytosis and T cell activation are uncoupled processes handled by TZM and DC respectively.
T Cell Zone Resident Macrophages Silently Dispose of Apoptotic Cells in the Lymph Node.
Specimen part
View SamplesHere we quantified the transcription start site usage in a WT strain (BY4741) and a ?set2 strain associated with the appearence of cryptic transcription start sites. Overall design: Transcription start site usage was quantified using the 5’cap sequencing aproach for S. cerevisiae strains. Biological duplicates were included.
A high-throughput ChIP-Seq for large-scale chromatin studies.
Cell line, Subject
View SamplesWe present single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11. Our study reveals the transcriptional dynamics occuring during endothelial to hematopoietic transition, the process responsible for the production of hematopoietic stem cells. Overall design: single-cell mRNA-Sequencing of various endothelial and hematopoietic populations isolated from the mouse embryonic aorta at E10 and E11
Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.
Specimen part, Cell line, Subject
View Samplescharacterize the molecular signature of PB-IMC in different stages of tumor development, thus possibly leading to a novel, sensitive and elegant approach for early cancer detection and surveillance. Overall design: Two types of cancer. For each type 4 groups (day 0, day 4, day 8, day 11), for each group 3 biological repeats
The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.
Specimen part, Cell line, Subject
View SamplesMutations within the catalytic domain of the histone methyltransferase (HMT) EZH2 have been identified in subsets of Non-Hodgkin Lymphoma (NHL) patients. These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We previously reported the discovery of a potent, selective, S-adenosyl-methionine-competitive and orally bioavailable small molecule inhibitor of EZH2, EPZ-6438. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) led to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent tumor growth inhibition and eradication of genetically altered NHL with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 day after stopping compound treatment in two EZH2 mutant xenograft models. These data confirm the dependency of mutant NHL on EZH2 activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.
Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma.
Cell line, Time
View SamplesNuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S -transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.
Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.
Sex, Age, Specimen part
View SamplesAll mRNA was isolated after 8 hours of culture time in each of three culture conditions. (1) TCPS Plate, (2) Collagen-GAG 2 dimensional coated plate and (3) collagen-GAG three dimensional mesh.
Fibroblast remodeling activity at two- and three-dimensional collagen-glycosaminoglycan interfaces.
No sample metadata fields
View SamplesThe goal of this study was to investigate the effects of vairous diets on the expression of genes involved in intermediary metabolism in liver. Adult wild type male mice (3 for each group) were fed with the corresponding diet for two weeks, and then liver samples were collected. Total RNA was isolated by the RNAzol B reagent, and pellet was disolved in DEPC-treated water. Total RNA was isolated using RNA Bee reagent (Tel-Test Inc., Friendswood, TX) per the manufacturers protocol. RNA concentrations were quantified using a NanoDrop Spectrophotometer (NanoDrop Technologies, Wilmington, DE) at a wavelength of 260 nm. The integrity of the total RNA samples was evaluated by formaldehyde-agarose gel electrophoresis, and confirmed by visualization of 18S and 28S rRNA bands. The gene expression was determined by Affymetrix Mouse 430 2.0 Gene Expression Microarray. Nine different diets were used: Diet 1. TD.84224. EFA Deficient diet; Diet 2. TD 97070. High fat diet: Diet 3. TD.88137. Adjusted Calories Diet (42% from fat) (Western Diet); Diet 4. TD.02028. Atherogenic Rodent Diet; Diet 5. TD.89247. 60% Fructose Diet; Diet 6. TD.94048. AIN-93M Purified Diet, Diet 7. Current rodent diet used in LAR; Diet 8. DHA-supplemented diet; Diet 9. Diet-restriction: 75% of the diet consumed by ad lib feeding. Mice (n=3/diet) were fed one of these diets (Harlan Laboratories) for 3 weeks. All mice were euthanized in the morning (8:0010:00 A.M.) and blood and tissue samples were collected. All procedures were approved in accordance with Institutional Animal Care and Use Committee guidelines.
Effect of diet on expression of genes involved in lipid metabolism, oxidative stress, and inflammation in mouse liver-insights into mechanisms of hepatic steatosis.
Sex, Age, Specimen part
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