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GSE13032
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Resiquimod is a nucleoside analog belonging to the imidazoquinoline family of compounds which is known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. Despite this demonstrated effectiveness, little is known about the molecular events responsible for this effect. The aim of the present study was to elucidate the molecular processes which were altered following resiquimod treatment and antigen challenge in a mouse model of allergic asthma. Employing microarray analysis, we have characterized the asthmatic transcriptome of the murine lung and determined that it includes genes involved in: the control of cell cycle progression, airway remodelling, the complement and coagulation cascades, and chemokine signalling. We have demonstrated that systemic resiquimod administration resulted in the recruitment of NK cells to the lungs of the mice, although no causal relationship between NK cell recruitment and treatment efficacy was found. Furthermore, results of our studies demonstrated that resiquimod treatment resulted in the normalization of the expression of genes involved with airway remodelling and chemokine signalling, and in the modulation of the expression of genes including cytokines and chemokines, adhesion molecules, and B-cell related genes, involved in several aspects of immune function and antigen presentation. Overall, our findings identified several genes, important in the development of asthma pathology, that were normalized following resiquimod treatment thus improving our understanding of the molecular consequences of resiquimod treatment in the lung milieu.
Publication Title
Modulation of the allergic asthma transcriptome following resiquimod treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The BcA86 strain is a unique recombinant congenic strain created from parental strains A/J and C57BL/6J. Naive mice from the BcA86 strain have a lung responsiveness phenotype resembling mice from airway hyperresponsive strain A/J. However, majority of the BcA86 genome is from the hyporesponsive strain C57BL/6J. Our goal was to identify the genomic regions that are associated with this BcA86 phenotype. Using F2 mice generated from BcA86 backcrossed to C57BL/6J, we identified a QTL for airway hyperresponsiveness on mouse chromosome 12. We validated the importance of mouse chromosome 12 in airway responsiveness using a chromosome 12 substitution strain (CSS12) which contains A/J chromosome 12 on a C57BL/6J background. The CSS12 strain also had a lung responsiveness phenotype similar to A/J. We selected genes within our QTL as candidates for airway hyperresponsiveness if they contained a deleterious coding variant (based on PROVEAN analysis) or if they were differently expressed between hyperresponsive (A/J, BcA86, CSS12) and hyporesponsive (C57BL/6J) strains.
Publication Title
Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Whole-genome sequencing recently identified recurrent missense mutations in the RNA helicase DDX3X in pediatric medulloblastoma (MB) and other tumors. The normal function of DDX3X is poorly understood, and the consequences of its cancer-associated mutations have not been explored. Here we used genomic, biochemical, cell biological, and animal modeling approaches to investigate normal DDX3X function and the impact of cancer-associated DDX3X mutations. Cross-linking immunoprecipitation–high-throughput sequencing (CLIPseq) analyses revealed that DDX3X binds primarily to ~1000 mature mRNA targets at binding sites spanning the full mRNA length; their enrichment in the coding regions suggests that DDX3X plays a role in translational elongation. The association of wild-type DDX3X with polysomes is consistent with this observation. Cancer-associated mutations result in loss of DDX3X from polysomes and accumulation of mutant DDX3X in stress granules (cytoplasmic accumulations of translationally arrested mRNAs). Mutation-dependent redistribution of DDX3X to stress granules is also observed in a Drosophila model system and in MB tumor cells from patients carrying DDX3X mutations. Importantly, mRNAs targeted by DDX3X are enriched in translation factors, suggesting that DDX3X regulates translation both directly and indirectly. Indeed, depletion of DDX3X by RNAi or over-expression of mutant DDX3X significantly impairs global protein synthesis. Ribosome profiling confirmed this observation and showed a 5’ bias in ribosomal occupancy, further confirming the role of DDX3X in translational elongation. Together, our data show that DDX3X is a key regulator of translation and that this function is impaired by cancer-associated mutations. Finally, we found that medulloblastoma-related mutant DDX3X can efficiently bind the wild-type form suggesting that mutant DDX3X could exert a dominant negative effect in vivo. Overall design: Examination of the whole tarnscriptome under conditions of DDX3X knockdown or overexpression of WT DDX3X or cancer-associated DDX3X mutants
Publication Title
Cancer-associated DDX3X mutations drive stress granule assembly and impair global translation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. To characterize transporter gene expression in NKCC1-/- mice, we examined the OE gene profile (Supplementary Table 1) using Illumina RNA-Seq to generate OE transcriptomes from NKCC1-/- and wild type mice. We analyzed RNA from OEs of male and female NKCC1+/+ (12 ± 1 weeks) and NKCC1-/- mice (16.5 ± 3.5 weeks, NMRI background); each RNA sample was prepared from an OE pool of 4 (mixed-gender pool RNA isolation) or 2 (gender RNA pool) different mice for each condition. Our data demonstrated the absence of a highly expressed ion transporter that could compensate for NKCC1. Overall design: The Illumina RNA-Seq protocol was utilized. In total, we amplified and sequenced up to 38 million 101 nt-long fragments from murine NKCC1+/+ and NKCC1-/- adult OEs.
Publication Title
Ion transporter NKCC1, modulator of neurogenesis in murine olfactory neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 140 Downloadable Samples
- IlluminaHiSeq2000
Description
C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2 arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. We have determined the binding sites and motifs of 119 C2H2 zinc finger proteins and the expression pattern of 80 cell lines overexpressing C2H2 zinc finger proteins in order to study the role of C2H2 zinc finger proteins in gene regulation. Overall design: We expressed GFP-tagged C2H2-ZF proteins in stable transgenic HEK293 cells. Total RNA was isolated using Trizol and sequencing libraries were constructed using TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold or TruSeq RNA Library Preparation Kit v2.
Publication Title
Multiparameter functional diversity of human C2H2 zinc finger proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The fetal ovarian grafts under the kidney capsule of adult male mice undergo a partial sex-reversal showing ectopic SOX9-positive Sertoli cell-like cells around 15-20 days post-transplantation. However, the molecular bases of such masculinization of fetal ovaries in the paternal environment were unclear.
Publication Title
Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long term survival of engrafting cells in the body, not only do the cells have to execute liverspecific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 postdifferentiation), hepatoblast (day 15) and immature hepatocytes (day 21) from human embryonic stem cells (hESC). Day 5, 15 and 21 cells were stimulated with IFN-a and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-a treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFNstimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatocytes upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs – LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. Overall design: 12 samples total, 4 samples in each time point (day 5, day 15, day 21). Each group of 4 within each time point has 2 control and 2 treatment samples in which the cells were stimulated with human interferon-alpha A (R and D Systems) at a concentration of 5000 IU for 6 hours.
Publication Title
Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The onset of the liver inflamentation in the Sox17+/- embryos.
Publication Title
Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Phosphatidylcholine transfer protein (PC-TP, a.k.a StarD2) is abundantly expressed in liver and is regulated by PPAR. When fed the synthetic PPAR ligand fenofibrate, Pctp-/- mice exhibited altered lipid and glucose homeostasis. Microarray profiling of liver from fenofibrate fed wild type and Pctp-/- mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. Because its expression controlled the transcriptional activities of both PPAR and HNF4 in cell culture, the broader impact of PC-TP on nutrient metabolism is most likely secondary to its role in fatty acid metabolism.
Publication Title
Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to validate the utility of a novel pathway algorithm (BD-Func), we test if an LBH589 signature based data from 3 cell lines (GSE36509) in an independent experiment in vivo.
Publication Title
BD-Func: a streamlined algorithm for predicting activation and inhibition of pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples