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SRP056103
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2000
Description
Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for b-cell loss since their b-cell–producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that b-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward b-cells in mouse and human. These effects are dynamic and correlate with functional b-cell regeneration when conditions allow. Overall design: Insulin-positive Glut2-low cell population of adult pancreatic tissue is enriched for PMP cells. Streptozocin (STZ) can enter beta-cells via Glut2 , induce cell death and consequently diabetes. Insulin-positive cells from two groups (STZ-injected experiment and vehicle-injected control, n=3/group) of MIP-GFP transgenic male mice were sorted to Glut2-low (Glut2L) and Glut2-high (Glut2H) by FACS. Total RNA from these samples were extracted for transcriptome analysis.
Publication Title
Diabetes enhances the proliferation of adult pancreatic multipotent progenitor cells and biases their differentiation to more β-cell production.
Sample Metadata Fields
No sample metadata fields
View Samples- Plasmodium falciparum
- 2 Downloadable Samples
Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
Investigations on the fundamental of malaria parasite biology, such as invasion, growth cycle, metabolism and cell signalling have uncovered a number of potential antimalarial drug targets, including choline kinase, a key enzyme involved in the synthesis of phosphatidylcholine, an important component in parasite membrane compartment.
Publication Title
Effect of choline kinase inhibitor hexadecyltrimethylammonium bromide on Plasmodium falciparum gene expression.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages
Publication Title
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Membrane estrogen receptor (ER) alpha stimulates AMP kinase to suppress SREBP1 processing and lipids in liver
Publication Title
Estrogen reduces lipid content in the liver exclusively from membrane receptor signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The leaf extract of T. indica had been reported to posses high phenolic content and showed high antioxidant activities. However, scientific data on the molecular mechanisms underlying the beneficial properties of the leaf extract are still lacking. In this study, the effects of the leaf extract on the expression of genes in cultured HepG2 cells were investigated using microarray technology. The leaf extract significantly regulated the expression of genes involved with consequential impact on the coagulation system, cholesterol biosynthesis, xenobiotic metabolism signaling and antimicrobial response.
Publication Title
Investigation into the effects of antioxidant-rich extract of Tamarindus indica leaf on antioxidant enzyme activities, oxidative stress and gene expression profiles in HepG2 cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligands activation of RXR modulate host antivarl response. We used microarray to determine if 9cRA could regulate the antiviral gene expression in LPS- and polyI:C triggered RAW264.7 cells.
Publication Title
Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
SRSF2 is an RNA binding protein that plays important roles in splicing of mRNA precursors. Mutations in SRSF2 are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how they affect SRSF2 function has only begun to be examined. Here we used CRISPR/Cas9 to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these, 374 involve the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more included exons and a distinct motif (UGGA/UG) in the more excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG, but less tightly to UGGAG sites. The pattern of exon inclusion or exclusion thus correlated in most cases with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings not only shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation, but also reveal a group of mis-spliced mRNA isoforms for potential therapeutic targeting. Overall design: Examination of differentially spliced events in K562 CRISPR cell clones (with wild-type or mutant SRSF2) by RNA sequencing
Publication Title
Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response program. We tested the hypothesis that a serum response program can be used to classify diseased tissues, and investigated the serum response program in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including RA, OA and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response program discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through 3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts.
Publication Title
Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We performed genome-wide expression profiling of cells infected with control or RPS14 shRNAs.
Publication Title
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown. Overall design: Retinas from rd7 and wild-type (C57BL/6J) mice at age 21 days were harvested. Two biological replicates per strain were collected. Each replicate consisted of 8 retinas total from two female and two male mice. RNA was extracted with Trizol, polyA-selected, and processed for mRNA-seq. All four samples were sequenced on a single lane of Illumina HiSeq 2000 (1x50 bp). Note that Nr2e3 transcript levels are higher in the rd7 mutant, as previously reported (Chen et al 2006 Hum Mol Genet 15(13):2146-56).
Publication Title
The role of retinol dehydrogenase 10 in the cone visual cycle.
Sample Metadata Fields
Age, Cell line, Subject
View Samples