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accession-icon GSE71124
Out-of-Sequence Signal 3 Paralyzes Primary CD4+ T Cell Dependent Immunity
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Primary T cell activation involves the integration of three distinct signals delivered in sequence: 1) antigen recognition, 2) costimulation, and 3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing bystander T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4+ T cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted nave CD4+ but not CD8+ T cells and was mediated through transient suppressor of cytokine signaling-3 (SOCS3) inhibition of the STAT5b transcription factor signaling pathway. These events resulted in complete paralysis of primary CD4+ T cell activation affecting memory generation, induction of autoimmunity, as well as impaired viral clearance. These data highlight the critical regulation of nave CD4+ T cells during inflammatory conditions.

Publication Title

Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity.

Sample Metadata Fields

Treatment

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accession-icon GSE37655
Gene expression alteration by macrophage depletion in IKK mutant mice
  • organism-icon Mus musculus
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

We generated Ikk-KA/KA knock-in mice (KA/KA), in which an ATP binding site of Ikk Lys 44 was replaced by alanine. The knock-in mice develop severe skin lesions and begin to die after 6 to 10 months. We also found lung SCCs in some of the mice. To study lung SCC development, we stabilize the skin condition by crossing KA/KA with Lori.Ikk transgenic mice to generate KA/KA-Lori.Ikk mice, which 100% spontaneously developed lethal lung SCC at 4 to 6 months of age.

Publication Title

The pivotal role of IKKα in the development of spontaneous lung squamous cell carcinomas.

Sample Metadata Fields

Age, Specimen part

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accession-icon SRP071332
Expression profiling of IL-13 stimulated PBMCs with and without an IL-13R antagonist
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

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.

Publication Title

Combining multiple tools outperforms individual methods in gene set enrichment analyses.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE2031
Identification of genes and quantitative trait loci (QTL) that control hematopoietic stem cell functioning
  • organism-icon Mus musculus
  • sample-icon 44 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

We 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.

Publication Title

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP090472
Morphological and molecular characterization of human dermal lymphatic collectors
  • organism-icon Homo sapiens
  • sample-icon 122 Downloadable Samples
  • Technology Badge Icon

Description

Millions 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.

Publication Title

Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE28644
Gene Expression Data Following Chronic Vehicle or Fluoxetine Treatment in Thirty Mouse Inbred Lines
  • organism-icon Mus musculus
  • sample-icon 60 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In 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.

Publication Title

Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP150419
Haemopedia: Human Haematopoietic Gene Expression
  • organism-icon Homo sapiens
  • sample-icon 84 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Database of gene expression in different haematopoietic cell types at haemosphere.org Overall design: Comparison of gene expression in different haematopoietic cell types

Publication Title

Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE76966
G-CSF receptor targeting in inflammatory arthritis
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

G-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.

Publication Title

Therapeutic Targeting of the G-CSF Receptor Reduces Neutrophil Trafficking and Joint Inflammation in Antibody-Mediated Inflammatory Arthritis.

Sample Metadata Fields

Sex, Specimen part, Disease, Disease stage, Treatment

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accession-icon GSE10246
GNF Mouse GeneAtlas V3
  • organism-icon Mus musculus
  • sample-icon 181 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

High-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

Publication Title

Expression analysis of G Protein-Coupled Receptors in mouse macrophages.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE48359
Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo
  • organism-icon Gallus gallus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Chicken Genome Array (chicken)

Description

A 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

Publication Title

Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo.

Sample Metadata Fields

Specimen part

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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