Filters
Technology
Platform
GSE18083
Mus musculus
7 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ragweed challenge in Ragweed (RWE) sensitized animals generates Reactive oxygen species (ROS) in the airway epithelium and induces allergic airway inflammation. We want to study the genes induced by ROS generated by RWE. This goal can be achieved by comparing PBS challenge vs. RWE challenge.
Publication Title
Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
NextSeq 500
Description
Use NGS-transcriptome profiling (RNA-seq) to investigate deregulated genes involved in the proliferative effects of ID-8 and Harmine after hypoxia-induced damage in primary human proximal tubular epithelial cells (HPTECs) Overall design: Examination of differentially expressed genes in HPTECs treated with 1uM of ID-8; or 1uM of Harmine; or EGF in comparison to cells without treatment after 24 hours of hypoxia, in triplicates
Publication Title
A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- NextSeq 500
Description
Secreted MOdular Calcium-binding protein-2 (SMOC2) belongs to the SPARC (Secreted Protein Acidic and Rich in Cysteines) family of matricellular proteins whose members are known for their secretion into the extracellular space to modulate cell-cell and cel Overall design: mRNA sequencing of mouse kidney of wildtype and Smoc2 transgenic mice with and without 7 day unilateral uretal obstruction intervention
Publication Title
Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Chronic kidney disease (CKD) is the gradual, asymptomatic loss of kidney function and current tests only identify it when significant loss has already happened. Using RNA sequencing in a mouse model of folic acid (FA) induced nephropathy, here we report the identification of 10 genes that track kidney fibrosis development, the common pathological finding in CKD patients. The gene expression of all 10 candidates was confirmed to be significantly high (~ 10-150 fold) in three well-established and mechanistically distinct mouse models of kidney fibrosis. Protein expression was also high in the FA model as well as patients with biopsy-proven kidney fibrosis. The specificity of these 10 candidates for kidney fibrosis was demonstrated by showing a very modest (~ 2-5 fold) increase in the mouse models of acute kidney injury as well as following liver fibrosis in mice and humans. Using targeted selected reaction monitoring mass spectrometry (SRM-MS) we found that 3 out of 10, cadherin 11 (CDH11), mannose receptor C1 (MRC1), phospholipid transfer protein (PLTP), are detectable in human urine. Furthermore, the levels of CDH11 and MRC1 are able to distinguish patients with chronic kidney disease from healthy individuals (n = 78, p<0.01). In summary, we report the identification of CDH11 and MRC1 as novel non-invasive biomarkers of CKD. Overall design: mRNA sequencing of mouse kidney before and at various time points (1,2,3,7 & 14 days) after intraperitoneal treatment with folic acid.
Publication Title
RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor- (TNF-) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
Publication Title
Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.
Sample Metadata Fields
Sex, Specimen part, Race, Subject
View Samples- Homo sapiens
- 73 Downloadable Samples
- NextSeq 500
Description
Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive, and thus, novel techniques, including human microphysiological systems, or “organs on chips,” are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; yet clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.2 ×10–16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)–like 2 pathway despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as the novel (to our knowledge) pathway for PMB- induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule. Overall design: Cells from six donors were seeded into a total of 74 kidney chips, and effluents of kidney MPS were exposed for 48 hours of treatments
Publication Title
Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tuberculosis remains a major cause of death from an infectious disease worldwide, yet only 10% of people infected with Mycobacterium tuberculosis develop disease. Defining both necessary and sufficient immunologic determinants of protection remains a great scientific challenge. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify human potential candidate markers of host defense by studying gene expression profiles of macrophages, cells which, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene co-expression network analysis revealed an association between the cytokine, IL-32, and the vitamin D antimicrobial pathway in a network of IFN- and IL-15 induced defense response genes. IL-32 was sufficient for induction of the vitamin D-dependent antimicrobial peptides, cathelicidin and DEFB4, and generation of antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. The IL-15 induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent vs. active tuberculosis or healthy controls, and a co-expression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15 induced gene network. Inferring that maintaining M. tuberculosis in a latent state and preventing transition to active disease represents host resistance, we believe these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.
Publication Title
IL-32 is a molecular marker of a host defense network in human tuberculosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity.
Publication Title
Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 4000, Illumina HiSeq 2000
Description
Gene expression analysis of purified thymopoiesis-initiating progenitors/early thymic progenitors, lymphoid primed multipotent progenitors (LMPP) and hematopoietic stem/progenitor cells from E11.5, E12.5, E13.5 embryos, neonatal (1 week old) and adult (8 weeks old) mice Overall design: Differentially expressed genes analysis
Publication Title
Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons
Publication Title
Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.
Sample Metadata Fields
No sample metadata fields
View Samples