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accession-icon GSE6055
Gene Expression Profiling Reveals Unique Pathways Associated with Differential Severity of Lyme Arthritis
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a)

Description

The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.

Publication Title

Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE16195
Expression profiling of joint tissue from C3H and interval specific congenic mouse lines post- B. burgdorferi infection
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Gene expression profile of joint tissue from C3H and interval specific congenic mouse lines (ISCL) following infection with Borrelia burgdorferi

Publication Title

Interval-specific congenic lines reveal quantitative trait Loci with penetrant lyme arthritis phenotypes on chromosomes 5, 11, and 12.

Sample Metadata Fields

Specimen part

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accession-icon SRP065478
Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.

Publication Title

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE2118
IR-response in Atm-/- and control lymph nodes
  • organism-icon Mus musculus
  • sample-icon 13 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

The DNA damage response network modulates a wide array of signaling pathways, including DNA repair, cell cycle checkpoints, apoptotic pathways and numerous stress signals. The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia (A-T), is a master regulator of this network when the inducing DNA lesions are double strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combines gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation (IR) in murine lymphoid tissue. Cluster analysis revealed six major expression patterns in the data. Prominent among them was a gene cluster that contained dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of the transcription factors NF-kB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and anti-apoptotic signals were simultaneously induced, with the pro-apoptotic pathway mediated by p53, and the pro-survival pathway by NF-kB. These findings further elucidate the molecular network induced by IR and have implications for cancer management as they suggest that a combined treatment that restores the p53-mediated apoptotic arm while blocking the NF-kB-mediated pro-survival arm could be most successful in increasing the radiosensitivity of lymphoid tumors.

Publication Title

Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP191447
Avidity Selection of Natural Killer Response to MCMV
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 4000

Description

Natural killer (NK) cells are innate lymphocytes that possess features of adaptive immunity, such as the ability to recognize specific antigen, among others. In MCMV infection, the engagement of a subset of NK cells expressing an activating receptor Ly49H with MCMV-derived glycoprotein m157 results in a clonal-like expansion and the generation of a small pool of long-lived memory cells with higher Ly49H expression than the naive Ly49H-expressing NK cell pool. In this study, we interrogate the transcriptional differences between NK cells that express high verus low levels of Ly49H early after infection. Overall design: RNASeq was performed on Ly49Hhi and Ly49Hlow NK cells harvested after 1.5 days post in vivo infection; 4 replicates per group and 50,000 cells per replicate.

Publication Title

Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE30747
AML mouse models
  • organism-icon Mus musculus
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE30746
Expression data from murine Tet-off MLL-AF9/Ras acute myeloid leukemia cell lines following withdrawal of MLL-AF9
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the Tet-off tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo.

Publication Title

An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.

Sample Metadata Fields

Specimen part, Treatment

View Samples
accession-icon GSE30745
Expression data from murine acute myeloid leukemia (AML) cells following shRNA-mediated suppression of Myb
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Using an integrative approach combining a Tet-off conditional AML mouse model, global expression profiling following suppression of the driving MLL-AF9 oncogene, and a new Tet-on conditional shRNA expression system we have identified Myb as critical mediator of addiction to MLL-AF9. Suppression of Myb in established AML in vivo terminates aberrant self-renewal and triggers a terminal myeloid differentiation program that precisely phenocopies the effects of suppressing MLL-AF9. Remarkably, suppressing Myb effectively eradicates aggressive and chemotherapy resistant AML.

Publication Title

An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.

Sample Metadata Fields

Specimen part

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accession-icon GSE107015
Gene expression data from whole blood of a Phase II randomized clinical trial of the treatment of methamphetamine dependence with topiramate
  • organism-icon Homo sapiens
  • sample-icon 209 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A genome-wide RNA expression study based on a Phase II randomized placebo-controlled clinical trial of topiramate (TPM) treatment of methamphetamine (METH) dependence.

Publication Title

Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction.

Sample Metadata Fields

Sex, Age, Specimen part, Treatment, Race, Subject, Time

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accession-icon SRP101281
Programed cell removal of Neutrophils regulated by calreticulin
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

RNA seq analysis for pathwayidentification to identify Overall design: RNA Seq analysis of apoptotic resistant and WT neutrophils isolated from bone marrow and peritoneum after thiglycollate induced inflammation

Publication Title

Programmed cell removal by calreticulin in tissue homeostasis and cancer.

Sample Metadata Fields

Specimen part, Cell line, Subject

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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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