Alveolar rhabdomyosarcomas (ARMS) are aggressive soft-tissue sarcomas affecting children and young adults. Most ARMS tumors express the PAX3-FKHR or PAX7-FKHR (PAX-FKHR) fusion genes resulting from the t(2;13) or t(1;13) chromosomal translocations, respectively. However, up to 25% of ARMS tumors are fusion negative, making it unclear whether ARMS represent a single disease or multiple clinical and biological entities with a common phenotype. To test to what extent PAX-FKHR determine class and behavior of ARMS, we used oligonucleotide microarray expression profiling on 139 primary rhabdomyosarcoma tumors and an in vitro model. We found that ARMS tumors expressing either PAX-FKHR gene share a common expression profile distinct from fusion-negative ARMS and from the other rhabdomyosarcoma variants. We also observed that PAX-FKHR expression above a minimum level is necessary for the detection of this expression profile. Using an ectopic PAX3-FKHR and PAX7-FKHR expression model, we identified an expression signature regulated by PAX-FKHR that is specific to PAX-FKHR-positive ARMS tumors. Data mining for functional annotations of signature genes suggested a role for PAX-FKHR in regulating ARMS proliferation and differentiation. Cox regression modeling identified a subset of genes within the PAX-FKHR expression signature that segregated ARMS patients into three risk groups with 5-year overall survival estimates of 7%, 48%, and 93%. These prognostic classes were independent of conventional clinical risk factors. Our results show that PAX-FKHR dictate a specific expression signature that helps define the molecular phenotype of PAX-FKHR-positive ARMS tumors and, because it is linked with disease outcome in ARMS patients, determine tumor behavior.
Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesRNA polymerase II is decreased on heat shock-induced genes when the CTD phosphatase Fcp1 is knocked down in Drosophila S2 cells. We examined transcriptionally-engaged Pol II genome-wide with GRO-seq to determine if other genes are similarly affected. Overall design: Two biological replicates of nascent RNA sequencing
Fcp1 dephosphorylation of the RNA polymerase II C-terminal domain is required for efficient transcription of heat shock genes.
Cell line, Subject
View SamplesHypertension remains a poorly understood condition, and the understanding of the sympathetic nervous systems role in this disease remains even more limited. In this study, RNA-sequencing is used to identify transcriptomal differences in the sympathetic stellate ganglia between the 16-week-old normotensive wistar strain and the spontaneously hypertensive rat strain.This dataset should allow for further molecular characterisation of hypertensive changes in a cardiac-innervating sympathetic ganglion. Overall design: Comparison of normotensive and hypertensive rat stellate ganglia. 4 biological replicates for both 16 week wistar and SHR stellate ganglia samples were contrasted
Neurotransmitter Switching Coupled to β-Adrenergic Signaling in Sympathetic Neurons in Prehypertensive States.
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View SamplesTranscriptome profiling using RNA-seq of ß-TC3 cell, a mouse pancreatic cell line used in the study of novel Cis-regulatory elements for the Pax6 gene . Overall design: Total RNA was collected and a Illumina sequencing libraries prepared from two biological replicates of cultured ß-TC3 cells.
Functional characteristics of novel pancreatic Pax6 regulatory elements.
Cell line, Subject
View SamplesBacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death.
Late multiple organ surge in interferon-regulated target genes characterizes staphylococcal enterotoxin B lethality.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Age, Specimen part
View SamplesThe effects of constitutively active Hypoxia Inducible Factor (HIF) and inactivated von Hippel-Lindau tumor suppressor gene product (pVHL) were examined in a mouse model. Conditionally expressed, constitutively active HIF-1a and HIF-2a were compared with inactivated pVHL.
Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo.
Specimen part
View SamplesUsing microdissected dendrites from primary cultures of hippocampal neurons of two mouse strains (C57BL/6 and Balb/c) and one rat strain (Sprague-Dawley), we investigate via microarrays, subcellular localization of mRNAs in dendrites of neurons to assay the evolutionary differences in subcellular dendritic transcripts localization.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Age, Specimen part
View SamplesMouse adult female brains cortex (C57BL/6, Charles River Laboratories, Inc.) was isolated and stored immediately at -80C. Subsequently, the mRNA (15g) was isolated using TRIzol Reagent and MicroFastTrack 2.0 Kit (Invitrogen). A Sample of 5g was assessed on Affymetrix Mouse 430.2 array. Aliquots from the leftovers of the same cortical mRNA were diluted to single-cell RNA levels (0.1, 1, and 10 pg) and independently aRNA amplified for a total of 2 and 4 rounds and assessed on Affymetrix Mouse 430.2 arrays.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Specimen part
View SamplesTo assess in order to assess potential disparities in gene expression due to developmental differences we performed a comparison between hippocampus and heart tissues from rat and mouse pup (one week old) and adult (10 week old) animals.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Age, Specimen part
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