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SRP181928
Rattus norvegicus
34 Downloadable Samples
NextSeq 550
Description
Nitrogen mustard (NM) is a vesicant known to target the lung, causing acute injury which progresses to fibrosis. Evidence suggests that activated macrophages contribute to the pathologic response to NM. In these studies, we analyzed the role of lung lipids generated following NM exposure on macrophage activation and phenotype. Treatment of rats with NM (0.125 mg/kg, i.t.) resulted in a time-related increase in enlarged vacuolated macrophages in the lung. At 28 d post exposure, macrophages stained positively for Oil Red O, a marker of neutral lipids. This was correlated with an accumulation of oxidized phospholipids in lung macrophages and epithelial cells, and an increase in bronchoalveolar lavage fluid (BAL) phospholipids. RNA-sequencing analysis revealed that lipid handling pathways under control of the transcription factors LXR, FXR and PPAR-? were significantly altered following NM exposure. Whereas at 1-3 d post NM, FXR and the downstream oxidized low density lipoprotein receptor, Cd36, were increased, Lxr and the lipid extrusion pump targets, Abca1 and Abcg1 were reduced. Treatment of naïve lung macrophages with lipid enriched fractions of BAL collected 3 d after NM resulted in upregulation of Nos2, Apoe and Ptgs2, markers of pro-inflammatory activation, while lipid-enriched BAL collected 28 d post NM upregulated expression of the anti-inflammatory markers, Il10, Cd163, and Cx3cr1, and induced the formation of lipid-laden foamy macrophages. These data suggest that NM-induced alterations in lipid handling and metabolism drive macrophage foam cell formation, potentially contributing to the development of pulmonary fibrosis. Overall design: Alveolar macrophages were collected by gentile message from male wistar rats 1 d or 28 d after intratracheal exposure to NM and from rats intratracheally exposed to PBS. There were three biological replicates per exposure group.
Publication Title
Regulation of Macrophage Foam Cell Formation During Nitrogen Mustard (NM)-Induced Pulmonary Fibrosis by Lung Lipids.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Messenger (m)RNA export from the nucleus is essential for eukaryotic gene expression. Here, we identify a transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, controlled by inositol polyphosphate multikinase (IPMK), an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. We studied transcripts encoding RAD51, a protein essential for DNA repair by homologous recombination (HR), to characterize the mechanism underlying IPMK-regulated mRNA export. IPMK depletion or catalytic inactivation selectively decreases the nuclear export of RAD51 mRNA, and RAD51 protein abundance, thereby impairing HR. Recognition of a sequence motif in the untranslated region of RAD51 transcripts by the mRNA export factor ALY requires IPMK. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), an IPMK product, restores ALY recognition in IPMK-depleted cell extracts, suggesting a mechanism underlying transcript selection. Our findings implicate IPMK in a transcript-selective mRNA export pathway controlled by phosphoinositide turnover that preserves genome integrity in humans.
Publication Title
Human inositol polyphosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
P3 Math1-nGFP mouse cochlear sensory epithelia, consisting of greater and lesser epithelial ridges (GER & LER) including the organ of Corti with nGFP-positive hair cells, were dissected, dissociated into single cells, and labeled with propidium iodide and three CD marker antibodies. The cell suspension was subjected to FACS purification. 83.6 2.8% of the total input of cells were viable, determined by exclusion of propidium iodide. Only viable cells were collected into 5 distinct populations: GFP+ cells (Samples HC_A-D), GFP/CD271High (Samples Mac_A-C), as well as GFP/CD271Low/CD326+/CD146Low (Samples SC_A-B), GFP/CD271Low/CD326+/CD146Hig (Samples GER_A-B), and GFP/CD271Low/CD326 (Sample BM_B). Please see Sinkkonen et al 2011 PMID: 22355545
Publication Title
Intrinsic regenerative potential of murine cochlear supporting cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC).
Publication Title
A Whole Blood Molecular Signature for Acute Myocardial Infarction.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Publication Title
The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Publication Title
The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 201 Downloadable Samples
- Illumina HiSeq 2500
Description
Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully re-capitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc, and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes . In addition, we observe a continuum of activation states, revealing a pseudo-temporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs,allowing for novel insights into neuronal activation patterns in vivo. Overall design: Examination of 1) 82 whole-cell (WC) dentate granule cells from a PTZ- or saline-treated mouse, and 2) 23 single-nuclei (SN) from dentate granule cells of a homecage (HC) mouse or 96 nuclei from a mouse exposed to a novel environment (NE)
Publication Title
Nuclear RNA-seq of single neurons reveals molecular signatures of activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation.
Publication Title
Functionally Distinct Subpopulations of CpG-Activated Memory B Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Overall design: Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates
Publication Title
Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Differential response to p300 inhibitor A-485 was observed in a panel of melanoma cell lines.
Publication Title
Targeting Lineage-specific MITF Pathway in Human Melanoma Cell Lines by A-485, the Selective Small-molecule Inhibitor of p300/CBP.
Sample Metadata Fields
Cell line, Treatment
View Samples