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SRP126482
Mus musculus
8 Downloadable Samples
Illumina HiSeq 3000
Description
Sustained spermatogenesis in adult males and recovery of fertility following germ cell depletion are dependent on undifferentiated spermatogonia with self-renewal potential. We have previously demonstrated a critical cell-autonomous role for Gilz in spermatogonial stem cell maintainance and spermatogenesis. To identify genes regulated by Gilz in the male germline, we have isolated undifferentiated spermatogonial cells from tamoxifen treated Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) mice that will allow identification of genes mis-expressed upon loss of GILZ. Overall design: 4 independent sets of Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) undifferentiated spermatogonia were isolated by flow sorting from adult mouse testes 7 days after treatment with tamoxifen.
Publication Title
GILZ-dependent modulation of mTORC1 regulates spermatogonial maintenance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a woundhealing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target.
Publication Title
Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray to look at the genes deregulated in PaTu8988s (adenovirus insensitive) and PaTu8988t (adenovirus sensitive) cell lines
Publication Title
CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The conditioned media from Bifidobacterium infantis (BCM) and Lactobacillus acidophilus (LCM) were reported to promote maturation of innate immune response gene expression, which explained the protective effects of probiotics in clinical necrotizing enterocolitis. We used microarray analysis to investigate the expression of genes involved in regulation of BCM and LCM in IL-1 stimulated immature human enterocytes.
Publication Title
Secreted Metabolites of Bifidobacterium infantis and Lactobacillus acidophilus Protect Immature Human Enterocytes from IL-1β-Induced Inflammation: A Transcription Profiling Analysis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 4000
Description
CD47 is a ubiquitous cell surface receptor that limits cell clearance by phagocytes that express its counter-receptor signal-regulatory protein-a and directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1. Murine natural killer (NK) cells express higher levels of CD47 than other lymphocytes, but the role of CD47 in regulating NK cell homeostasis and immune function remains unclear. Cd47-/- mice exhibited depletion of NK precursors in bone marrow, but antisense Cd47 knockdown or gene disruption resulted in a dose dependent accumulation of immature and mature NK cells in spleen. Cd47-/- mice were impaired in controlling chronic Clone-13 lymphocytic choriomeningitis virus (LCMV) infection, which was associated with depletion of splenic NK cells and loss of effector cytokine and interferon response gene expression in Cd47-/- NK cells. These data identify CD47 as a cell-intrinsic and systemic regulator of NK cell homeostasis and NK cell responses to viral infection. Overall design: Examining natural killer (NK) cell intrinsic role of CD47 during viral infection.
Publication Title
CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Malignant glioblastoma (GBM) is a highly aggressive brain tumor with a dismal prognosis and limited therapeutic options. Genomic profiling of GBM samples in the TCGA database has identified four molecular subtypes (Proneural, Neural, Classical and Mesenchymal), which may arise from different glioblastoma stem-like cell (GSC) populations. In the present study, we identify two GSC populations that produce GBM tumors by subcutaneous and intracranial injection with identical histological features. Gene expression analysis revealed that xenografts of GSCs grown as spheroid cultures had a Classical molecular subtype similar to that of bulk tumor cells. In contrast xenografts of GSCs grown as adherent cultures on laminin-coated plates expressed a Mesenchymal gene signature. Adherent GSC-derived xenografts had high STAT3 and ANGPTL4 expression as well as enrichment for stem cell markers, transcriptional networks and pro-angiogenic markers characteristic of the Mesenchymal subtype. Examination of clinical samples from GBM patients showed that STAT3 expression was directly correlated with ANGPTL4 expression, and that increased expression of these genes correlated with poor patient survival and performance. A pharmacological STAT3 inhibitor abrogated STAT3 binding to the ANGPTL4 promoter and exhibited anticancer activity in vivo. Taken together, we identified two distinct GSC populations that produce histologically identical tumors but with very different gene expression patterns, and a STAT3/ ANGPTL4 pathway in glioblastoma that may serve as a target for therapeutic intervention.
Publication Title
Molecular heterogeneity in a patient-derived glioblastoma xenoline is regulated by different cancer stem cell populations.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antibodies to self-nucleic acids, immune complex deposition and tissue inflammation such as glomerulonephritis. Innate recognition of molecular complexes containing self-DNA and RNA and the ensuing production of type I interferons (IFN) contribute to SLE development. Plasmacytoid dendritic cells (pDCs) have been proposed as a relevant source of pathogenic IFN in SLE; however, their net contribution to the disease remains unclear. We addressed this question using haplodeficiency of the pDC-specific transcription factor E2-2 (Tcf4), which causes a specific impairment of pDC function in otherwise normal animals. We report that Tcf4+/- animals were significantly protected from SLE-like disease caused by the overexpression of the endosomal RNA sensor Tlr7. The protection was also observed after the monoallelic deletion of Tcf4 specifically in the dendritic cell lineage. Furthermore, Tcf4 haplodeficiency in the B6.Sle1.Sle3 multigenic model of SLE ameliorated key disease manifestations including anti-DNA antibody production, immune activation and glomerulonephritis. These results provide genetic evidence that pDCs are critically involved in SLE pathogenesis, confirming their potential utility as therapeutic targets in the disease.
Publication Title
Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute and chronic infectious diseases remains unclear. We recently demonstrated that IFN-??? receptor (IFNAR) signaling promotes Treg function in autoimmunity. To dissect the functional role of IFNAR-signaling in Tregs during acute and chronic viral infection, we infected Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice with LCMV Armstrong and Clone-13. In both models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced expression of Treg associated activation antigens. The enhanced activated phenotype was also seen when we compared the transcriptomes of IFNARfl/flxFoxp3YFP-Cre and wild type (WT) Tregs by RNA-Seq on day 25-post Clone-13 infection. LCMV-specific CD8+ T cells from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral IFN? and TNF? in both acute and chronic LCMV. In the chronic model, the numbers of anti-viral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs than WT mice during chronic infection. Thus, type I IFN signaling in Tregs is context-dependent, resulting in enhanced suppressor function in some models of autoimmunity, but decreased suppressor function in acute and chronic viral infection. Overall design: mRNA from Treg cells from 5 WT and 5 IFNAR deficient mice were analyzied by RNA-seq using Illumina HiSeq
Publication Title
Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
There are no effective treatments or clinical response markers for systemic sclerosis (SSc). We sought to assess the potential of novel imaging biomarkers and gene expression profiling approaches in a clinical trial of the tyrosine kinase inhibitor dasatinib in SSc patients with interstitial lung disease (SSc-ILD).
Publication Title
Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Gene expression analysis of a unique HNSCC (Head and Neck Squamous Cell Carcinoma) localization, the hypopharynx. Four normal and 34 tumor samples were analysed using Affymetrix HG-U95A microarrays containing probe sets representing ~12650 distinct transcription features.
Publication Title
Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples