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GSE79387
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- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to assess the physiological role of Cop1 in vivo we generated mice that do no longer express the protein. Cop1KO mice die at around E10.5 of embryonic development. In order to gain insights into the molecular mechanisms that cause the embryonic death we compared the genome-wide gene expression profile of E9.5 wild-tytpe and Cop1-null embryos. The data do not support a role for Cop1 in the regulation of the p53 pathway in vivo and highlight a role for Cop1 in cardiovascular development and/or angiogenesis. The abstract of the associated publication is as follows:Biochemical data have suggested conflicting roles for the E3 ubiquitin ligase Cop1 in tumourigenesis. Here we present the first in vivo investigation of the role of Cop1 in cancer aetiology. We used an innovative genetic approach to generate an allelic series of Cop1 and show that Cop1 hypomorphic mice spontaneously develop malignancy at a high frequency in their first year of life and are highly susceptible to radiation-induced lymphomagenesis. Biochemically, we show that Cop1 regulates c-Jun oncoprotein stability and modulates c-Jun/AP1 transcriptional activity in vivo. Cop1-deficiency stimulates cell proliferation in a c-Jun-dependent manner. We conclude that Cop1 is a tumour suppressor that antagonizes c-Jun oncogenic activity in vivo.
Publication Title
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
We used RNA sequencing to study gene expression in lymph node derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3, during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least two-fold changes. Almost three quarters of these increased during anaphylaxis Overall design: 5 Female Balb/c mice aged 4-5 weeks, were sensitized to peach using intranasally administered Pru p 3 in combination with LPS and challenged intraperitoneally as described previously . 5 Littermates, treated with intranasally administered PBS (instead of Pru p 3 and LPS), and later given an intraperitoneal challenge as per the anaphylactic mice, were used for comparison.
Publication Title
Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food-Antigen-Induced Anaphylaxis Reveals the Upregulation of Multiple Immune-Related Pathways.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Macaca mulatta
- 12 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Luteolysis of the corpus luteum (CL) during non-fertile cycles involves a cessation of progesterone (P4) synthesis (functional regression) and subsequent structural remodeling. The molecular processes responsible for initiation of luteal regression in the primate CL are poorly defined. Therefore, a genomic approach was utilized to systematically identify differentially expressed genes in the rhesus macaque CL during spontaneous luteolysis. CL were collected prior to (days 10-11 post-LH surge, mid-late [ML] stage) or during (days 14-16, late stage) functional regression. Based on P4 levels, late stage CL were subdivided into functional late (FL, serum P4 > 1.5 ng/ml) and functionally-regressed late (FRL, serum P4 < 0.5 ng/ml) groups (n=4 CL/group). Total RNA was isolated, labeled and hybridized to Affymetrix genome microarrays that contain elements representing the entire rhesus macaque transcriptome. With the ML stage serving as the baseline, there were 681 differentially expressed transcripts (>2-fold change; p< 0.05) that could be categorized into three primary patterns of expression: 1) increasing from ML through FRL, 2) decreasing from ML through FRL, and 3) increasing ML to FL, followed by a decrease in FRL. Ontology analysis revealed potential mechanisms and pathways associated with functional and/or structural regression of the macaque CL. Quantitative real-time PCR was used to validate microarray expression patterns of 13 genes with the results being consistent between the two methodologies. Protein levels were found to parallel mRNA profiles in 4 of 5 differentially expressed genes analyzed by Western blot. Thus, this database will facilitate the identification of mechanisms involved in primate luteal regression.
Publication Title
Dynamic changes in gene expression that occur during the period of spontaneous functional regression in the rhesus macaque corpus luteum.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 104 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
Publication Title
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.
Sample Metadata Fields
Sex, Specimen part, Disease, Race
View Samples- Macaca mulatta
- 18 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The molecular and cellular processes required for development, function, and regression of the primate corpus luteum (CL) are poorly defined. We hypothesized that there are dynamic changes in gene expression occurring during the CL lifespan, which represent proteins and pathways critical to its regulation. Therefore, a genomic approach was utilized to systematically identify differentially expressed genes in the rhesus macaque CL during the luteal phase of natural menstrual cycles. CL were collected between days 3-5 (early stage), 7-8 (mid), 10-12 (mid-late), 14-16 (late), or 18-19 (very-late) after the midcycle LH surge. From the early through very-late stages, 3234 transcripts were differentially expressed, with 879 occurring from the early through late stages that encompass the processes of luteinization, maintenance, and functional regression. To characterize gene changes most relevant to these processes, ontology analysis was performed using the list of 879 differentially expressed transcripts. Four main groups of related genes were identified with relevance to luteal physiology including: 1) immune function; 2) hormone and growth factor signaling; 3) steroidogenesis; and 4) prostaglandin biosynthesis, metabolism, and signaling. A subset of genes representing each of the four major categories was selected for validation of microarray results by quantitative real-time PCR. Results in mRNA levels were similar between the two methodologies for 17 of 18 genes. Additionally, protein levels for 3 genes were determined by Western blot analysis to parallel mRNA levels. This database will facilitate the identification of many novel or previously underappreciated pathways that regulate the structure and function of the primate CL.
Publication Title
Systematic determination of differential gene expression in the primate corpus luteum during the luteal phase of the menstrual cycle.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is increasingly appreciated that properties of cultured epithelial cells differ dramatically in 2D compared to 3D, and the latter more faithfully recapitulates in vivo behavior. By studying a battery of human colorectal cancer (CRC) cell lines in type-1 collagen, we have found that HCA-7 cells form colonies with two distinctive and persistent morphological and functional properties. We observed predominantly single-layered polarized cysts (cystic colonies, CC) and a smaller fraction displaying disorganized solid masses (spiky colonies, SC) that were highly invasive in vivo. Despite overall genomic similarity, CC and SC exhibited distinct and dynamic patterns of gene expression in 3D.
Publication Title
Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of biologically relevant enhancers in human erythroid cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina human-6 v2.0 expression beadchip
Description
Identification of cell-type specific enhancers is important for understanding the regulation of programs controlling cellular development and differentiation. Enhancers are typically marked by the co-transcriptional activator protein p300 or by groups of cell-expressed transcription factors. We hypothesized that a unique set of enhancers regulates gene expression in human erythroid cells, a highly specialized cell type evolved to provide adequate amounts of oxygen throughout the body. Using chromatin immunoprecipitation followed by massively parallel sequencing, genome-wide maps of candidate enhancers were constructed for p300 and four transcription factors, GATA1, NF-E2, KLF1, and SCL, using primary human erythroid cells. These data were combined with gene expression analyses and candidate enhancers identified. Consistent with their predicted function as candidate enhancers, there was statistically significant enrichment of p300 and combinations of co-localizing erythroid transcription factors within 1-50 kb of the TSS of genes highly expressed in erythroid cells. Candidate enhancers were also enriched near genes with known erythroid cell function or erythroid cell phenotypes. Candidate enhancers exhibited only moderate conservation with mouse and minimal conservation with nonplacental vertebrates. Candidate enhancers were mapped to a data set of erythroid-associated, biologically relevant, SNPs from the GWAS catalog of the NHGRI. Fourteen candidate enhancers, representing 10 genetic loci, mapped to sites associated with biologically relevant erythroid traits. Fragments from these loci directed statistically significant expression in reporter gene assays. Identification of enhancers in human erythroid cells will allow a better understanding of erythroid cell development, differentiation, structure, and function, and provide insights into inherited and acquired hematologic disease.
Publication Title
Identification of biologically relevant enhancers in human erythroid cells.
Sample Metadata Fields
Specimen part
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