Human medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
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View SamplesBACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Specimen part
View SamplesWe sought to find a gene-expression multigene predictor of response to infliximab therapy in Rheumatoid Arthritis patients. Using internal and external cross-validation systems we have built and validated an 8-gene predictor for response to infliximab.
An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.
Sex, Specimen part, Disease, Disease stage
View SamplesWe describe 9 CLL patients who underwent a spontaneous clinical regression. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6/8 cases, with the usage of V4-1 gene in 3. Microarray analysis of CLL cells revealed a distinctive genomic profile. The number of activated T lymphocytes expressing IFN-, TNF- and IL-4 was similar between CLL in spontaneous regression and healthy individuals.
Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesThis series contains re-analyzed samples from GSE39555, GSE39556 and GSE15907.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. These events occur independtly of type I interferons and of the microlofora, since the same maturation pattern is observed in XCR1+ tDcs from control, Ifnar1-KO and germ-free mice. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesDendritic cells (DC) play critical roles in central and peripheral T cell tolerance. DC found in the steady-state periphery undergo an homeostatic, tolerogenic, maturation that promotes interaction with naive T cells and induction of abortive responses. In contrast, thymic DC are thought to exist solely in an immature state. In this study, we show that XCR1+ thymic DC constitutively mature into a stage characterized by high levels of molecules involved in T cell activation. This unanticipated mature stage corresponded to a third of the XCR1+ thymic DC and fully accounted for their ability to cross-present self-antigens to developing T cells. Transcriptomic analysis of the XCR1+ DC found in thymus and steady-state periphery revealed that their maturation involves profound and convergent changes. Unexpectedly, maturation resulted in down-regulation of genes conferring their specific function on XCR1+ DC. Paradoxically, upon maturation, central and peripheral tolerogenic XCR1+ DC up-regulated many genes thought to drive pro-inflammatory T-cell responses. Thus, our results reveal that thymic XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating for both central and peripheral tolerance induction by XCR1+ DC.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
View SamplesXCR1+ dendritic cells (DC) have been shown to excel in antigen cross-presentation for the activation of nave CD8 T cells. This property was reported to be associated to the subset of the XCR1+ DC expressing IL-12b upon ex vivo stimulation for 24 h with a mixture of CpG, IFN-, and GM-CSF (Lin ML et al. Proc Natl Acad Sci USA. 2008. PMID: 18272486). DC found in the steady-state non-lymphoid tissues undergo an homeostatic, tolerogenic, maturation and migrate to the draining lymph nodes to interact with naive autoreactive T cells and induction their peripheral tolerance. In contrast, spleen DC are thought to exist solely in an immature state. The aim of this study was to re-examine heterogeneity within steady state spleen XCR1+ DC, in particular examining whether this population encompass a fraction of mature DCs as assessed through their expression of CCR7 and/or the Il12b gene. Indeed, we show that a small fraction of XCR1+ spleen DC constitutively mature into two distinct but likely successive activation stages characterized as CCR7+ and CCR7+Il12b+ respectively, and correlated with increasing ability to cross-present antigen to nave CD8 T cells. Transcriptomic analysis of the subsets of XCR1+ DC found in steady state spleen unexpectedly showed that their homeostatic maturation was unexpectedly associated with up-regulated of many genes thought to drive pro-inflammatory T-cell responses and previously found to be commonly induced upon maturation of distinct DC subsets in response to stimulation by various microbial-type stimuli (Vu Manh TP et al. Eur J Immunol. 2013. PMID: 23553052). Thus, our results reveal that spleen XCR1+ DC undergo constitutive maturation and emphasize the common mechanisms operating upon homeostatic, tolerogenic, DC maturation versus microbial-type stimuli-induced, immunogenic, DC maturation.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part
View SamplesThe goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of spleen XCR1+ DC early after MCMV infection in vivo, using on Affymetrix Mouse Gene 1.0 ST Array.
Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
Specimen part, Treatment
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