This experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). Overall design: The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.
Combining multiple tools outperforms individual methods in gene set enrichment analyses.
No sample metadata fields
View SamplesWe have combined large-scale mRNA expression and gene mapping methods to identify genes and loci that control hematopoietic stem cell (HSC) functioning. mRNA expression levels were measured in purified HSC isolated from a panel of densely genotyped recombinant inbred mouse strains. Quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts were mapped. Comparison of the physical transcript position with the location of the controlling QTL identified polymorphic cis-acting stem cell genes. In addition, multiple trans-acting control loci were highlighted that modify expression of large numbers of genes. These groups of co-regulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of strong candidate genes involved with HSC turnover. We compared expression QTLs in HSC and brain from the same animals, and document both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of co-regulated transcripts.
Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.
No sample metadata fields
View SamplesMillions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE-1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRa, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors a2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy. Overall design: The transcriptome of 6 different normal human lymphatic collectors (Lyko1, Lyko 4-12, Lyko 5, Lyko12, Lyko13, Lyko26) from the dermis of the thigh of women between 44 and 61 years of age was compared to cultures of human dermal lymphatic endothelial cells (LEC1, LEC2, HD-LEC9A) and a mixture of 3 different human dermal blood endothelial cells (HD-BEC-CA) to identify potential drug targets in the media of the collectors.
Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors.
No sample metadata fields
View SamplesThe goal of this study is to analyzed transcriptome changes caused by POLA1 deficiency. Our data represents the first detailed analysis of molecular basis of XLPDR syndrome. We report than POLA1 deficiency leads to over-activation of IRF and NF-kB pathways with overexpression of typical markers of autoimmune syndromes. Overall design: Wild type and XLPDR-derived dermal fibroblasts are analyzed under non-stimulated (basal) conditions, after TNF treatment (2 and 12 h, 1000 U/mL), and poly(dA:dT) stimulation (16h, 1 mkg/mL). Obtained data were confirmed using the cellular model of XLPDR - normal dermal fibroblasts pretreated with control or anti-POLA1 siRNA and stimulated in analogous way.
NK cell defects in X-linked pigmentary reticulate disorder.
No sample metadata fields
View SamplesIn order to understand how biochemical and genetic differences correlate with treatment response, we measured depressive-like behavior, gene expression and the levels of thirty-six neurobiochemical analytes across a panel of genetically-diverse mouse inbred lines after chronic treatment with vehicle or fluoxetine. Neurobiochemical markers were chosen based on their putative molecular function within pathways proposed to underlie depression, which include neuronal transmission, HPA-axis regulation, and neuroimmune processes. The goal of this study is to establish genetic and biochemical biomarkers that can predict treatment response and to propose a molecular pathway that is critical in mediating anti-depressant response.
Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains.
Sex, Specimen part
View SamplesDatabase of gene expression in different haematopoietic cell types at haemosphere.org Overall design: Comparison of gene expression in different haematopoietic cell types
Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans.
Specimen part, Subject
View SamplesG-CSF is a hemopoietic growth factor that has a role in steady state granulopoiesis, as well as in mature neutrophil activation and function. We developed a neutralizing monoclonal antibody to the murine G-CSF receptor (G-CSFR), which antagonizes binding of murine G-CSF and inhibits G-CSFR signalling. Anti-G-CSFR rapidly halts the progression of established disease in collagen antibody-induced arthritis (CAbIA). Neutrophil accumulation in joints is inhibited, without rendering animals neutropenic, suggesting an effect on homing to inflammatory sites. Neutrophils in the blood and arthritic joints of anti-G-CSFR treated mice show alterations in cell adhesion receptors, while anti-G-CSFR suppresses local production of proinflammatory cytokines and chemokines known to drive tissue damage. Our aim in this study was to use differential gene expression analysis of joint and blood neutrophils to more thoroughly understand the effect of G-CSFR blockade on the inflammatory response following anti-G-CSFR therapy in CAbIA.
Therapeutic Targeting of the G-CSF Receptor Reduces Neutrophil Trafficking and Joint Inflammation in Antibody-Mediated Inflammatory Arthritis.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesHigh-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we profiled gene expression from a diverse array of normal tissues, organs, and cell lines in mice. Keywords: multiple tissues
Expression analysis of G Protein-Coupled Receptors in mouse macrophages.
No sample metadata fields
View SamplesA systematic survey of the transcriptional status of individual segments of the developing chick hindbrain (r1-5) and the adjacent region of the embryonic midbrain (m) during the HH11 stage of chick development
Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo.
Specimen part
View SamplesThe tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.
A gene atlas of the mouse and human protein-encoding transcriptomes.
No sample metadata fields
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