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SRP168642
Homo sapiens
24 Downloadable Samples
Ion Torrent S5
Description
Systemic juvenile idiopathic arthritis (SJIA) is a chronic childhood arthropathy with features of autoinflammation. Early inflammatory SJIA is associated with expansion and activation of neutrophils with a sepsis-like phenotype, but neutrophil phenotypes present in longstanding and clinically inactive disease (CID) are unknown. The objective of this study was to examine activated neutrophil subsets, S100 alarmin release, and gene expression signatures in children with a spectrum of SJIA disease activity. Methods: Highly-purified neutrophils were isolated using a two-step procedure of density-gradient centrifugation followed by magnetic-bead based negative selection prior to flow cytometry or cell culture to quantify S100 protein release. Whole transcriptome gene expression profiles were compared in neutrophils from children with both active SJIA and CID. Results: Patients with SJIA and active systemic features demonstrated a higher number of CD16+CD62Llo neutrophil population compared to controls. This neutrophil subset was not seen in patients with CID or patients with active arthritis not exhibiting systemic features. Using imaging flow cytometry, CD16+CD62Llo neutrophils from patients with active SJIA and features of macrophage activation syndrome (MAS) had increased nuclear hypersegmentation compared to CD16+CD62L+ neutrophils. Serum levels of S100A8/A9 and S100A12 were strongly correlated with peripheral blood neutrophil counts. Neutrophils from active SJIA patients did not show enhanced resting S100 protein release; however, regardless of disease activity, neutrophils from SJIA patients did show enhanced S100A8/A9 release upon PMA stimulation compared to control neutrophils. Furthermore, whole transcriptome analysis of highly purified neutrophils from children with active SJIA identified 214 differentially expressed genes compared to neutrophils from healthy controls. The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4. Interestingly, this gene set showed intermediate levels of expression in neutrophils from patients with long-standing CID yet persistent serum IL-18 elevation. Indeed, all patient samples regardless of disease activity demonstrated elevated inflammatory gene expression, including inflammasome components and S100A8. Conclusion: We identify features of neutrophil activation in SJIA patients with active disease and CID, including a proinflammatory gene expression signature, reflecting persistent innate immune activation. Taken together, these studies expand understanding of neutrophil function in chronic autoinflammatory disorders such as SJIA. Overall design: Highly purified neutrophils isolated from patients with SJIA and healthy controls
Publication Title
Neutrophils From Children With Systemic Juvenile Idiopathic Arthritis Exhibit Persistent Proinflammatory Activation Despite Long-Standing Clinically Inactive Disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of major groups of AML fusion oncogenes on primary human CD34+ cells.
Publication Title
In vitro transformation of primary human CD34+ cells by AML fusion oncogenes: early gene expression profiling reveals possible drug target in AML.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG binding protein 2. MeCP2 is a transcriptional repressor elevated in mature neurons and is predicted to be required for neuronal maturation by regulating multiple target genes. Identifying primary gene targets in either Mecp2-deficient mice or human RTT brain has proven to be difficult, perhaps because of the transient requirement for MeCP2 during neuronal maturation. In order to experimentally control the timing of MeCP2 expression and deficiency during neuronal maturation, human SH-SY5Y cells undergoing mature neuronal differentiation were transfected with methylated MeCP2 oligonucleotide decoy to disrupt the binding of MeCP2 to endogenous targets. Genome-wide expression microarray analysis identified all four known members of the inhibitors of differentiation or inhibitors of DNA binding (ID1, ID2, ID3 and ID4) subfamily of helix-loop-helix (HLH) genes as novel neuronal targets of MeCP2. Chromatin immunoprecipitation analysis confirmed binding of MeCP2 near or within the promoters of ID1, ID2 and ID3, and quantitative RT-PCR confirmed increased expression of all four Id genes in Mecp2-deficient mouse brain. All four ID proteins were significantly increased in Mecp2-deficient mouse and human RTT brain using immunofluorescence and laser scanning cytometric analyses. Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT.
Publication Title
Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human T-cell leukemia virus type 1 (HTLV-1) encodes HTLV-1 bZIP factor (HBZ), which is thought to be crucial for neoplastic and inflammatory diseases caused by HTLV-1. So, we analyzed the transcriptional profile of HBZ expressing cells and how HBZ affect the expression of apoptosis-related genes.
Publication Title
HTLV-1 bZIP factor suppresses apoptosis by attenuating the function of FoxO3a and altering its localization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer can be divided in two major histological subtypes: diffuse and intestinal-type adenocarcinomas. Since both types diverge in many clinical and molecular characteristics, is widely accepted that both represent distinct disease entities that may benefit from different therapeutic approaches. The diffuse type is explicitly more invasive and affected patients possess extremely poor prognosis. Gene expression profiling studies identified numerous genes with differences in mRNA expression between the two types. However, little overlap of published gene lists exists forcing the need for further and more comprehensive analyses.
Publication Title
THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Schizosaccharomyces pombe
- 3 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
An branched-chain amino acids auxotroph eca39 mutant fission yeast exhibits an unusual adaptive growth phenotype on solid minimal media containing Ile, Leu and Val when other strains are growing nearby.
Publication Title
The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 70 Downloadable Samples
- Illumina Genome Analyzer II, Illumina HiSeq 2000
Description
Meiosis is a complex developmental process that generates haploid cells from diploid progenitors. We measured mRNA abundance and protein production through yeast sporulation and found strong temporal control for most genes, achieved through both mRNA levels and translational regulation. Monitoring the timing of protein production revealed novel factors involved in recombination and helped to illuminate the molecular basis of the broad restructuring of meiotic cells. We also found a strong increase in noncanonical translation at short open reading frames (sORFs) on unannnotated transcripts and upstream regions of known transcripts (uORFs). Ribosome occupancy at near-cognate uORFs was associated with more efficient ORF translation; while some AUG uORFs, often on regulated leader extensions, acted comptetitively. This work reveals a pervasive role for meiotic translational control and great complexity in genomic coding. Overall design: Fine mapping of gene expression through meiosis reveals extensive regulation of protein synthesis and widespread non-canonical translation.
Publication Title
High-resolution view of the yeast meiotic program revealed by ribosome profiling.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HiSeq 3000
Description
Understanding how differentiation, microenvironment, and hormonal milieu influence human breast cell susceptibility to malignant transformation will require the use of physiologically relevant in vitro systems. We developed a 3D culture model that enables the propagation of normal estrogen receptor alpha (ER)+ cells. The purpose of this experiment was to assess ER functionality and compare estrogen-induced transcripts among samples and systems. Overall design: RNA-seq was performed on RNA prepared from replicate 3D cultures from 3 normal 3D breast culture specimens exposed to 10nM estradiol or vehicle alone for 6 or 24 hours.
Publication Title
Propagation of functional estrogen receptor positive normal human breast cells in 3D cultures.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, and thereby cause IgE-mediated food allergy.
Publication Title
Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
We performed global scale microarray analysis to identify detailed mechanisms by which nonpermissive temperature induces cell growth arrest and differentiation in astrocyte RCG-12 cells harboring temperature-sensitive simian virus 40 large T-antigen by using an Affymetrix GeneChip system. Astrocyte RCG-12 cells used in this study were derived from primary cultured rat cortical glia cells infecting with a temperature-sensitive simian virus 40 large T-antigen. Although the cells grew continuously at the permissive temperature, the nonpermissive temperature led to cell growth arrest and differentiation. Of the 15,923 probe sets analyzed, nonpermissive temperature differentially expressed 556 probe sets by >2.0-fold.
Publication Title
Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line RCG-12.
Sample Metadata Fields
No sample metadata fields
View Samples