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Mus musculus
20 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stage-specific sensitivity to p53 restoration during lung cancer progression.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumor-suppressor pathways. The quest to personalize cancer medicine based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumor suppressors and activation of oncogenes are required for tumor maintenance. Mutations in the p53 tumor-suppressor pathway are a hallmark of cancer and significant efforts toward pharmaceutical reactivation of mutant p53 pathways are underway1-3. Here we show that restoration of p53 in established murine lung tumors leads to significant but incomplete tumor cell loss specifically in malignant adenocarcinomas but not in adenomas. Also, we define amplification of MAPK signaling as a critical determinant of malignant progression. The differential response to p53 restoration depends on activation of the Arf tumor suppressor downstream of hyperactive MAPK signaling. We propose that p53 naturally limits malignant progression by responding to increased oncogenic signaling, but is unresponsive to low levels of oncogene activity that are sufficient for early stages of lung tumor development. These data suggest that restoration of pathways important in tumor progression, as opposed to initiation, may lead to incomplete tumor regression due to the stage-heterogeneity of tumor cell populations.
Publication Title
Stage-specific sensitivity to p53 restoration during lung cancer progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumor-suppressor pathways. The quest to personalize cancer medicine based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumor suppressors and activation of oncogenes are required for tumor maintenance. Mutations in the p53 tumor-suppressor pathway are a hallmark of cancer and significant efforts toward pharmaceutical reactivation of mutant p53 pathways are underway1-3. Here we show that restoration of p53 in established murine lung tumors leads to significant but incomplete tumor cell loss specifically in malignant adenocarcinomas but not in adenomas. Also, we define amplification of MAPK signaling as a critical determinant of malignant progression. The differential response to p53 restoration depends on activation of the Arf tumor suppressor downstream of hyperactive MAPK signaling. We propose that p53 naturally limits malignant progression by responding to increased oncogenic signaling, but is unresponsive to low levels of oncogene activity that are sufficient for early stages of lung tumor development. These data suggest that restoration of pathways important in tumor progression, as opposed to initiation, may lead to incomplete tumor regression due to the stage-heterogeneity of tumor cell populations.
Publication Title
Stage-specific sensitivity to p53 restoration during lung cancer progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response.
Publication Title
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
Publication Title
Expression profiling reveals metabolic and structural components of extraocular muscles.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE13765- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. While there are some well-characterized examples, the vast majority (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here, we report a new approach to identifying large non-coding RNAs (ncRNAs) by using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified ~1600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening ncRNAs (lincRNAs) exhibit strong purifying selection in their genomic loci, exonic sequences, and promoter regions with greater than 95% showing clear evolutionary conservation. We also developed a novel functional genomics approach that assigns putative functions to each lincRNA, revealing a diverse range of roles for lincRNAs in processes from ES pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFKB, Sox2, Oc4, and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
Publication Title
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 30 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use
Publication Title
Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques.
Sample Metadata Fields
Specimen part, Time
View Samples- Danio rerio
- 68 Downloadable Samples
IlluminaHiSeq2000
Description
Zebrafish of two different age groups (12 and 36 months) were treated with low amounts of rotenone (mild stress) and compared to untreated zebrafish. Two different durations were used (3 and 8 weeks). Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 68 sample: 3 tissues (brain, liver, skin); 2 age groups (12 and 36 months); controls and rotenone treated samples; 2-6 biological replicates for each group
Publication Title
Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Ocular growth is regulated locally by signals produced in the retina that ultimately act on the growth of the scleral tissue. Consequently, a number of studies have investigated changes in retinal gene expression during manipulation of ocular growth in an attempt to elucidate the biochemical pathways underlying eye growth. However, due to the highly heterogenous nature of the retina, important changes in gene expression can be masked. Therefore, this study has investigated changes in gene expression specifically within the retinal amacrine cell layer, the most likely generator of growth signals, during manipulations of ocular growth.
Publication Title
Gene expression within the amacrine cell layer of chicks after myopic and hyperopic defocus.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 47 Downloadable Samples
- IlluminaHiSeq2500
Description
RNA-seq was performed to compare expression pattern of musles taken form two mice strains- mdx and mdx/Runx1f/f, which are double KO carrting a muscle specific ablation of Runx1 using a Myf5-Cre. This comparison revealed the Runx1- responsive gene set in mdx muscles. we could cross this data with prior retrived datd from privous experiments found in this GEO quary, to pinpiont Runx1 target genes in muscle rgeneration Overall design: RNA was extracted form soleus muscles of 2 months old mice, n=3,4 for mdx and mdx/Runx1f/f, respectively . Differentially expressed genes were discovered using the DeSeq2 software
Publication Title
Genomic-wide transcriptional profiling in primary myoblasts reveals Runx1-regulated genes in muscle regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples