Filters
Technology
Platform
Anopheles gambiae
104 Downloadable Samples
Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
Anopheles gambiae,the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis ofA. gambiaehead and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.
Publication Title
Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus, Homo sapiens
- 21 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Pentraxin-2 (PTX-2) is a constitutive, anti-inflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Recent studies indicate that systemic delivery of recombinant PTX-2 inhibits inflammatory diseases associated with fibrosis by blocking pro-fibrotic macrophage activation and promoting anti-inflammatory and regulatory macrophages. Here we show that recombinant human PTX-2 (rhPTX-2) retards the progression of chronic kidney disease in Col4a3 mutant mice that develop Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously-delivered rhPTX-2 is detected in macrophages but is also found in tubular epithelial cells where it counteracts macrophage activation and is cytoprotective for the epithelium. We performed transcriptional profiling of whole kidney homogenates and human proximal tubule epithelial cells (PTECs) to identify pathways differentially activated or suppressed in response to treatment with PTX-2. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun and its binding partners, which form AP-1 complexes, as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun activation and reduces expression of AP-1 dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting.
Publication Title
Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The long term goal is to define the transcriptional changes that accompany pericyte-to-myofibroblast transition in fibrotic kidney disease. Medullary pericytes are identified by their expression of a eGFPL10a fusion protein whose expression is driven by a Col1a1 promoter. Pericyte-specific RNA is generated by eGFP-affinity purification of polysomes from medullary lysates and then subject to microarray analysis.
Publication Title
Translational profiles of medullary myofibroblasts during kidney fibrosis.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Kidney peritubular capillaries are particularly susceptible to rarefaction and regeneration-limited after exposure to toxins or injuries. Studying these kidney microvessels remain challenging, primarily resulting from difficulties imaging in vivo, as well as isolating and culturing kidney microvascular cells in vitro, in particular in a three-dimensional (3D) microenvironment with proper hemodynamics. Here, we developed methods to isolate, purify, and characterize human kidney peritubular microvascular endothelial cells (hKMECs), and reconstituted a 3D kidney microvasculature in collagen matrix. Compared to other endothelial cells, isolated hKMECs are very sensitive to VEGF for survival and growth, and have a high vasculogenic but low angiogenic potential. Under flow, they formed a fenestrated endothelium with a comprehensive permeability barrier. When exposed to calcineurin inhibitors, hKMECs formed microvessels displayed cell retraction, broken fenestrae, and swollen endothelium, which led to a thrombogenic luminal wall and erythrocytes extravasations into the subendothelial space. Our study recapitulated the human kidney microvascular structure and function, and shed lights on potential mechanistic studies of kidney specific injuries and diseases.
Publication Title
A Novel Three-Dimensional Human Peritubular Microvascular System.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina HiSeq 2500
Description
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
Publication Title
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Inhibition of FOXO1 activity in kidney microvascular endothelial cells improves angiogenesis Overall design: Kidney microvascular endothelial cells were serum starved and treated with DMSO control or FOXO1 inhibitor for one hour, then stimulated with VEGF for 30 minutes
Publication Title
Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: MicroRNA-21 contributes to the pathogenesis of fibrogenic diseases in multiple organs including the kidney. To evaluate the therapeutic utility of antimiR-21 oligonucleotides in chronic kidney disease, we silenced miR-21 in mice that develop Alport Nephropathy due to a defect in the Col4a3 gene. The goals of this study to assess the effect of inhibiting miR-21 in the Col4a3-/- Alport Syndrome mouse model at 5.5 weeks of age. Methods: Col4a3-/-, Col4a3+/-, and Col4a3+/+ mice in the 129X1/SvJ genetic background were obtained. Mice received anti–miR-21 (25 mg/kg) or control anti-miR (25mg/kg) in phosphate-buffered saline (PBS) by inter-scapular subcutaneous injection twice per week. In some experiments mice received a range of doses from 12.5mg/kg once a week to 50mg/kg once a week. Anti–miR-21 is a high-affinity oligonucleotide complementary to the active site of miR-21. Mice received injections starting at 24 days (3.5 weeks) after birth and ending at 5, 7, 9 or 16 weeks after birth depending on the study objectives. Total RNA from kidney tissue was extracted as per manufacturer’s instructions (miREASY kit, Qiagen). RNA quality was assessed using BioAnalyzer (Agilent). mRNA expression profiles were determined using next-generation sequencing (NGS) on the Illumina HiSeq 2000 platform producing 50bp paired-end reads. Bowtie/TopHat suites were used to align the reads to mouse genome or transcriptome and RSEM were used to quantify gene abundances. Gene level counts were then normalized with the R/Bioconductor package limma using the voom/variance stabilization method. Results: Anti-miR-21 enhanced PPARa/RXR activity and associated downstream signaling pathways in glomerular, tubular and interstitial cells, enhanced mitochondrial function, which reduced mitochondrial ROS production and preserved tubular cell functions. In addition, inhibition of miR-21 reduced fibrogenic and inflammatory signaling in glomerular and interstitial cells, likely as a consequence of enhanced PPARa/RXR activity and mitochondrial function. Inhibition of miR-21 represents a novel therapeutic strategy for chronic kidney diseases including Alport Nephropathy. Overall design: Whole kidney mRNA profiles of Col4a3+/- (triplicate) and Col4a3-/- (quadruplicates) mice treated with either PBS or antimiR-21, ending at 5.5 weeks of age, were generated by Next Generation Sequencing using Illumina HiSeq 2000
Publication Title
Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic inflammation during placental malaria (PM) caused by Plasmodium falciparum is most frequent in first-time mothers and is associated with poor maternal and fetal outcomes. In the first genome wide analysis of the local human response to sequestered malaria parasites, we identified genes associated with chronic PM, then localized the corresponding proteins and immune cell subsets in placental cryosections.
Publication Title
Genome-wide expression analysis of placental malaria reveals features of lymphoid neogenesis during chronic infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
We describe a chemical method to label and purify 4-thiouridine (s4U) -containing RNA. We demonstrate that methanethiolsulfonate (MTS) reagents form disulfide bonds with s4U more efficiently than the commonly used HPDP-biotin, leading to higher yields and less biased enrichment. This increase in efficiency allowed us to use s4U-labeling to study global microRNA (miRNA) turnover in proliferating cultured human cells without perturbing global miRNA levels or the miRNA processing machinery. This improved chemistry will enhance methods that depend on tracking different populations of RNA such as 4-thiouridine-tagging to study tissue-specific transcription and dynamic transcriptome analysis (DTA) to study RNA turnover. Overall design: s4U metabolic labeling of RNA in 293T cells, followed by biochemical enrichment of labeled RNA with two biotinylation reagents, RNAs >200nt and miRNAs in separate experiments
Publication Title
Tracking Distinct RNA Populations Using Efficient and Reversible Covalent Chemistry.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE12247- Mus musculus
- 54 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The mammary gland develops mainly postnatally, when during pregnancy the epithelium grows out into the mammary fat pad and forms a network of epithelial ducts. During pregnancy, these ducts branch and bud to form alveoli. These alveoli produce the milk during lactation. After 7 days of lactation, involution was induced by force weaning the pups. The newly formed epithelium undergoes apoptosis and is removed from the tissue by neighbouring epithelial cells. Tissue remodelling leads to a morphology resembling a gland of a pre-pregnant mouse. Microarray analysis was used to measure mRNA expression of genes during puberty, pregnancy, lactation and involution in a Balb/c mouse strain.
Publication Title
Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3.
Sample Metadata Fields
No sample metadata fields
View Samples