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GSE48027
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Publication Title
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 65 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence, however, indicates that sleep is necessary for normal brain function and that the need to sleep is a tightly regulated process. Surprisingly molecular mechanisms that determine the need to sleep are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need.
Publication Title
Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
The in vitro effect of infection with different strains of Toxoplasma gondii was tested 24 hours after infection of Human Foreskin Fibroblasts (HFF)
Publication Title
Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 25 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II () interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (/) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II () interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (/) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
Publication Title
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA.
Publication Title
Chondrocyte cultures from human proximal interphalangeal finger joints.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Transposable elements make up nearly half of mammalian genomes, yet are generally described as 'junk DNA' or genome parasites. The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, but it is paradoxically expressed at high levels during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem (ES) cells and pre-implantation embryos. In ES cells, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a gene expression program specific to the 2-cell stage. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, thereby promoting rRNA synthesis and ES cell self-renewal. In embryos, LINE1 RNA is required for silencing of Dux, proper synthesis of rRNA and exit from the 2-cell stage. These results reveal an essential partnership between nuclear LINE1 RNA and chromatin factors in the regulation of transcription, developmental potency and ES cell self-renewal. Overall design: 3 replicates each of E14 ES cells two days after nucleofection with Lissaminated ASOs - RC (control) or LINE1, purified according to Lissamine+ using flow cytometry then lysed for RNA extraction and library generation (6 samples total)
Publication Title
A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to detail the global programme of gene expression underlying the effect of sleep deprivation in the mouse hippocampus and identified distinct classes of regulated genes during this process.
Publication Title
Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN). However, the mechanism by which mutant CALR is oncogenic is unknown. Here, we demonstrate that a megakaryocytic-specific MPN phenotype is induced when mutant CALR is over-expressed in mice and that the thrombopoietin receptor, MPL is required for mutant CALR driven transformation. Whole transcriptome analysis reveals enrichment of STAT signatures in mutant CALR transformed cells and JAK2 inhibitor treatment abrogates STAT activation. Employing extensive mutagenesis-based structure-function analysis we demonstrate that the positively charged amino acids within the mutant CALR C-terminus are required for cellular transformation through facilitating physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel mechanism of cancer pathogenesis. Overall design: Transcriptomes derived from BA/F3-MPL cells transformed with human wild-type CALR, human mutant CALR 52bp del, or Empty vector, at time zero (t0) and 24 hours (t24) after IL3-withdrawal culture were generated by deep sequencing, two replicas, by HiSeq2000.
Publication Title
Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation.
Sample Metadata Fields
Cell line, Subject
View Samples