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SRP082142
Mus musculus
8 Downloadable Samples
NextSeq 500
Description
The balance between protecting tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection using a combined genomic and proteomic approach. We followed the transcriptional dynamics and ECM- related responses in a mouse model of influenza virus infection, integrated with whole tissue imaging and functional assays. Our study identifies MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza virus infection. We show that selective inhibition of MT1-MMP-driven ECM proteolysis protects the tissue from infection-related structural and compositional damage. Inhibition of MT1-MMP did not significantly alter the immune response or cytokine expression, indicating its dominant role in ECM remodeling. We demonstrate that the available treatment for influenza virus (Tamiflu/ Oseltamivir) does not prevent lung ECM damage and is less effective than anti-MT1-MMP treatment in influenza virus and Streptococcus pneumoniae coinfection paradigms. Importantly, combination therapy of Tamiflu with anti-MT1-MMP shows a strong synergistic effect and results in complete recovery in mice. This study highlights the importance of tissue tolerance agents for surviving infectious diseases, and the potential of such host-pathogen therapy combination for respiratory infections. Overall design: Overall 8 samples were included, in duplicates, both infected and non-infected control cells were includeda. Both MT1-MMP positive and MT1-MMP negative were tested were non-infectdd, MT1-MMP negative cells served as controls.
Publication Title
Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- NextSeq 500
Description
It is well established that the expression profiles of multiple and possibly redundant matrix remodeling proteases (e.g. collagenases) strongly differ in health, disease and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in-vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), generated uniquely by individual homologous proteases, leads to specific combinatorial events, which eventually affects overall ECM topography, visco-elastic properties and composition. We reveal striking differences in the movement and signaling patterns, morphology, and gene expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, unlike envisioned before matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. As ECM proteolysis is an abundant biochemical process critical to tissue homoeostasis, these results improve our fundamental understanding of combinatorial factors dictating cell behavior. Overall design: We analyzed the transcriptional responses of fibroblasts interacting with MMP1 or MMP13-remodeled ECM 4 hours post seeding. Samples used: Fibroblasts interacting with MMP1-remodeled ECM; Fibroblasts interacting with MMP13-remodeled ECM; Control samples- Fibroblasts interacting with natural ECM. All samples were run in duplicates.
Publication Title
Distinct biological events generated by ECM proteolysis by two homologous collagenases.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 48 Downloadable Samples
- NextSeq 500
Description
Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein (HSD) or that has been supplemented with a rich source of saturated fat (HFD). These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline, such as decreased climbing ability. We subjected Oregon-R-C flies to variants of the HSD, HFD, or normal (control) diet (ND), followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. We targeted at least 50 million paired-end, stranded reads of 75 basepairs in size, and analyzed 4 biological replicates per dietary condition. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Functional annotation and enrichment analysis among genes whose expression was significantly affected by the obesogenic diets indicated an overrepresentation of genes associated with immunity, metabolism, and hemocyanin in the HFD group, and CHK, cell cycle activity, and DNA binding and transcription in the HSD group. Heat map representation of genes affected by both diets illustrated a large fraction of differentially expressed genes between the two diet groups. Diets high in sugar and diets high in fat both have notableeffects on the Drosophila transcriptome in head tissue. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation. Our results also indicate differences in the effects of the HFD and HSD on expression profiles in head tissue of Oregon-R-C flies, despite the reportedly similar phenotypic impacts of the diets. Overall design: Flies were reared on one of three diets (high fat, high sugar, or normal). 6 replicates, with twenty flies each, from each diet treatment were collected for a total of 18 samples. The heads of the flies were then obtained, and RNA extracted from each of those samples. 4 of the RNA samples from each diet group (12 samples total) were sequenced.
Publication Title
RNA-Sequencing of <i>Drosophila melanogaster</i> Head Tissue on High-Sugar and High-Fat Diets.
Sample Metadata Fields
Specimen part, Subject
View Samples- Glycine max
- 71 Downloadable Samples
- NextSeq 500
Description
Gene expression of the F1 Hybrids between two soybean parents (NMS4-44-329 and N7103) were compared. Changes in gene expression were correlated with agronomic traits. Overall design: RNA was isolated from leaf matrial harvested from the field in july of 2015. Four replicates were grown at two location in a random complete block design. Each samples is represented from three or four replications form each location
Publication Title
Changes in gene expression between a soybean F1 hybrid and its parents are associated with agronomically valuable traits.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The outcome of infections with Toxoplasma gondii in humans is dependent in part on the genetic makeup of the infecting organism. Recent studies have indicated that most infecting Toxoplasma organisms fall into 1 of 3 canonical lineages. Previous studies have investigated the effects of Toxoplasma on its host cell transcriptome. Little is known, however, about the effects of three canonical lineages on brain cells, the principal site of parasite lifelong persistence. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to T. gondii infection using microarray analysis to characterize the strain-specific host cell response to 3 canonical T. gondii strains. We found that the extent of the expression changes varied considerably among the three strains. Neuroepithelial cells infected with type I exhibited the most differential gene expression, whereas type II infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to central nervous system while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter expression of a clearly defined set of genes. Moreover, Ingenuity pathway analysis (IPA) revealed the sophistication of different strain in its interactions with the host. These differences may explain some of the variation in the neurobiological effects of different strains of Toxoplasma on infected individuals.
Publication Title
Differential effects of three canonical Toxoplasma strains on gene expression in human neuroepithelial cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Smyd3 is a histone methyltransferase implicated in tumorigenesis. Here we show that Smyd3 expression in mice is required but not sufficient for chemically induced liver and colon cancer formation. In these organs Smyd3 is functioning in the nucleus as a direct transcriptional activator of several key genes involved in cell proliferation, epithelial-mesenchymal transition, JAK/Stat3 oncogenic pathways, as well as of the c-myc and b-catenin oncogenes. Smyd3 specifically interacts with H3K4Me3-modified histone tails and is recruited to the core promoter regions of many but not all active genes. Smyd3 binding density on target genes positively correlates with increased RNA Pol-II density and transcriptional outputs. The results suggest that Smyd3 is an essential transcriptional potentiator of a multitude of cancer-related genes. Overall design: Standard Smyd3-deficient (Smyd3-KO) mice were generated using gene-trap ES cell clones (AS0527 from International Gene Trap Consortium), in which a selection cassette, containing the splice acceptor site from mouse EN2 exon 2 followed by the beta-galactosidase and neomycin resistance gene fusion gene and the SV40 polyadenylation sequence was inserted into the 5th intron of the Smyd3 gene. The resulting mice were devoid of Smyd3 mRNA and protein in all tissues, including liver and colon. For the generation of Smyd3-Tg mice the open reading frame of the mouse Smyd3 cDNA, which contained 3 Flag epitopes at the 3’ end was inserted into the StuI site of the pTTR1-ExV3 plasmid (Yan et al, 1990). The 6.8 kb HindIII fragment containing the mouse transthyretin enhancer/promoter, intron 1, Smyd3 cDNA, three Flag epitopes and SV40 poly-A site was used to microinject C57Bl/6 fertilized oocytes. Founder animals were identified by Southern blotting and crossed with F1 mice to generate lines. Specific overexpression in the liver was tested by RT-PCR analysis in different tissues.
Publication Title
Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Transactive response DNA-binding protein of 43 kDa (TDP-43), a heterogeneous nuclear ribonucleoprotein (hnRNP) with diverse activities, is a common denominator in several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Orthologs of TDP-43 exist from mammals to invertebrates, but their functions in lower organisms remain poorly understood. Here we systematically studied mutant Caenorhabditis elegans lacking the nematode TDP-43 ortholog, TDP-1. To understand the global gene expression regulation induced by the loss of tdp-1, the C. elegans transcriptomes were compared between the N2 WT animals and the tdp-1(ok803lf) mutant. Transcriptional profiling demonstrated that the loss of TDP-1 altered expression of genes functioning in RNA processing and protein folding. These results suggest that the C. elegans TDP-1 as an RNA-processing protein may have a role in the regulation of protein homeostasis and aging.
Publication Title
Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 218 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Investigation of gene expression profiles among patients with COPD frequent exacerbations and to find gene targets as predictors of exacerbations
Publication Title
Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2500
Description
We report RNA sequencing data from tenocytes treated with IGF1. Tenocytes were obtained from the tail tendons of adult C57Bl/6 mice via collagenase digestion. Tenocytes were grown to 60% confluence, and then treated with 100ng/mL of recombinant IGF1 for a period of 0, 1, 2, 6, or 24 hours. Experiments were conducted in quadruplicate. RNA was isolated and prepared for RNA sequencing. Overall design: Differential expression of mRNAs were evaluated from tenocytes isolated from tail tendons of adult wild type C57Bl/6 mice that were treated with recombinant IGF1 for 0, 1, 2, 6, and 24 hours.
Publication Title
Insulin-like growth factor 1 signaling in tenocytes is required for adult tendon growth.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Regulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Publication Title
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Sample Metadata Fields
Age, Specimen part
View Samples