Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part due to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to easily assess tumor samples for degree of anaplasia. Instead, identification of genetic signatures able to distinguish among anaplastic grades and thus predict high versus low risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia would also yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes are also able to accurately predict severe anaplasia in our dataset. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.
Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.
Specimen part
View SamplesDetailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Age, Specimen part, Treatment
View SamplesLocal mRNA translation mediates the adaptive responses of axons to extrinsic signals but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles suggesting distinct steps in axon wiring, such as elongation, pruning and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and novel sequence elements generated by alternative splicing that promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo. Overall design: The profiling of ribosome-bound mRNAs in mouse retinal ganglion cell axons at 4 different developmental stages
On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
No sample metadata fields
View SamplesAJ mouse is susceptible to lung carcinogenesis from urethane treatment and is a good model for human adenocarcinoma. We completed a study using microarray analysis of bronchoalveolar lavage cells from control or urethane treated mice. A unique macrophage expression signature in the lung tumor microenvironment was able to correctly classify the lavage samples.
A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
No sample metadata fields
View SamplesSubstantial experimental evidence has shown that dedifferentiation from an epithelial state to a mesenchymal-like state (EMT) drives tumor cell metastasis. This transition facilitates tumor cells to acquire motility and invasive features. Intriguingly, tumor cells at the metastatic site are primarily epithelial, and it is believed that they re-differentiate back to an epithelial state by a process called mesenchymal to epithelial transition (MET). However, there is little in vivo evidence to support the MET process.
E-cadherin re-expression shows in vivo evidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells.
Specimen part, Cell line
View SamplesPurpose: Tracheal epithelial brush cells are rare chemosensory cells defined by their expression of elements of the bitter taste transduction system, and known to activate the cholinergic nervous system in the murine lung. Similar chemosensory cells in the intestine can generate lipid mediators and pro-inflammatory cytokines but whether brush cell can contribute to airway inflammation is unknown. Furthermore, despite the advances in understanding chemosensory cell effector functions, the receptors that mediate chemosensory cell activation and expansion beyond taste receptors in any compartment remain largely unknown. Methods: In this study, we isolated tracheal brush cells by FACS from naïve ChATBAC-eGFP mice with knockin of eGFP within a BAC spanning the acetylcholine transferase locus, marking brush cells in the epithelium and performed transcriptome profiling using low input RNA sequencing. We compared tracheal brush cells to EpCAM+ epithelial cells and CD45+ hematopoetic cells in naive mice. Results: When compared to EpCAM+ EpCs and to CD45+ cells in the airway, principal component analysis demonstrated that brush cells grouped quite distinctly. This brush cell distinction relative to EpCAM+ cells, was further reflected in the striking number of highly differentially expressed genes. This included 1305 genes expressed at 4-fold or higher levels in EpCAM+eGFP+ cells (brush cells), of which 418 genes were expressed at 32-fold or higher levels in brush cells. Conclusions: Our study represents the first detailed analysis of the transcriptome of tracheal brush cells and identifies a unique set of genes that are primarily expressed in brush cells including the bitter taste transduction system, synthenic machinery for several pro-inflammatory lipid mediators and HoxA2 transciptional factors. Overall design: Examination of gene expression of tracheal brush cells (ChAT-eGFP), EpCAM+ (EpCAM) tracheal epithelial cell and CD45+ hematopoetic cells in naïve mice.
The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing airway brush cells leading to type 2 inflammation.
Specimen part, Cell line, Subject
View SamplesImmune indicators of PDAC progression were obtained from peripheral blood and analyzed in the context of each other by calculating a serum-induced transcriptome index and a serum cytokine index. Significant correlation of the transcriptome index with the inflammatory transcriptome index suggest that inflammtion has a role in PDAC progression. The segregation of metastatic progressed and not progressed patients when the inflammatory transcriptome index was analyzed in the context of the serum cytokine index suggest that the serum cytokine index may be a systemic biomarker of PDAC progression . Our data illustrates both the transcriptome and cytokine indices have promise as biomarkers of cancer immunity.
A Serum-Induced Transcriptome and Serum Cytokine Signature Obtained at Diagnosis Correlates with the Development of Early Pancreatic Ductal Adenocarcinoma Metastasis.
Specimen part
View SamplesLung tumors
Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model.
No sample metadata fields
View SamplesMET expression is elevated in a majority of human skin cancers but its contributions to pathogenesis have not been evaluated. In a mouse model of constitutive overexpression of HGF (MT-HGF), the incidence of squamous cell skin tumors induced by initiation with 7,12-dimethylbenz(a)anthracene (DMBA) followed by exposure to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is increased fivefold over control groups. Half of these tumors carry Hras1 or Kras mutations. Without DMBA initiation, tumors also erupt on MT-HGF mouse skin but only when TPA promotion is enhanced by crossing these mice with mice overexpressing cutaneous PKC. None of these tumors have Ras mutations. In culture, MT-HGF keratinocytes share identical MET mediated phenotypic and biochemical features with wildtype keratinocytes transformed by oncogenic RAS. In both cell types, these common features of initiated keratinocytes arise from autocrine activation of EGFR through elevated expression and release of EGFR ligands. Inhibition of EGFR ablates the initiated signature of MT-HGF keratinocytes in vitro and causes regression of MT-HGF induced tumors in vivo. Global gene expression data indicate that MT-HGF and RAS transformed keratinocytes share largely an identical profile of over 5000 mRNAs. Gene ontology analysis reveals the most affected concordant signature is enriched for functions relevant to tissue development and response to wounding, accompanied by cytokine and growth factor activity, and peptidase and endopeptidase activity previously not linked to initiated keratinocytes. Furthermore, gene co-expression analysis in skin cancer patients revealed a core RAS/MET co-expression network considerably activated in pre cancerous and cancerous lesions. Thus MET activation though EGFR contributes to human cutaneous cancers, and inhibitors could be efficacious in advanced lesions such as those seen in transplant recipient patients.
MET signaling in keratinocytes activates EGFR and initiates squamous carcinogenesis.
Specimen part
View Samples