A high percentage of uveal melanoma patients develop metastatic tumors that predominately occur in the liver. To identify genes associated with metastasis in this pathology, we studied 63 molecular profiles derived from gene expression microarrays performed from enuceated primary tumors.
High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients.
Sex, Age, Specimen part
View SamplesSomatic ribosomal protein defects have recently been described in cancer, yet their impact on cellular transcription and translation remain poorly understood. Here we integrated mRNA sequencing, ribosome footprinting, polysomal RNA seq and quantitative mass spectrometry datasets obtained from an isogenic mouse lymphoid cell model in order to study the T-cell acute lymphoblastic leukemia (T-ALL) associated R98S mutation in ribosomal protein L10 (RPL10 R98S). RPL10 R98S induced changes in protein levels were to a much larger extent caused by transcriptional then translational changes and RPL10 R98S cells showed a gene signature corresponding to deregulation of hematopoietic transcription factors. Phosphoserine phosphatase (PSPH), a key enzyme in serine biosynthesis, displayed elevated transcription and translation and was one of the proteins showing the strongest upregulation in RPL10 R98S cells. Increased Psph protein levels were confirmed in RPL10 R98S engineered JURKAT cells and in hematopoietic cell cultures derived from Rpl10 R98S knock-in mice. Moreover, elevated serine and glycine biosynthesis in RPL10 R98S cells was supported by metabolic flux analyses. Analysis of PSPH expression levels in T-ALL patient samples revealed that PSPH upregulation is a generalized phenomenon in this disease, associated with elevated circulating serine and glycine levels. Addition of serine and glycine enhanced survival of stromal and myeloid cells, suggesting supportive effects on the hematopoietic niche. Finally, reduction of PSPH expression levels in T-ALL cell lines suppressed their in vitro proliferation and their capacity to expand in T-ALL xenograft models. In conclusion, transcriptome, translatome and proteome analysis of the RPL10 R98S mutation identified RPL10 R98S driven induction of cellular serine biosynthesis. Whereas serine metabolism has been implicated in cancer via PHGDH amplification, this is the first report supporting dependence of ALL cells on the serine biosynthesis enzyme PSPH. Overall design: 3 biological replicates for each condition (RPL10 R98S, RPL10 WT)
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells.
Specimen part, Subject
View SamplesThe study was designed in order to identify genes differentially expressed when glucocorticoid signaling is blocked by a glucocorticoid-receptor antagonist (RU486 mifepristone) in the context of brain inflammation induced by bacterial lipopolysaccharide (LPS). LPS is only able to cause murine brain damage in our experimental conditions upon RU486 pre-treatment. Hence, the study may reveal potential candidate genes to mediate neuroprotection or neurotoxicity. Due to the factorial design of the experiment, RU486 main-effect could be dissociated from the effects resultant of RU486/inflammation interaction. In addition, brain dissection was conducted to verify the effects in the brain side ipsilateral or contralateral to the site of intracerebral LPS infusion.
Genes involved in the balance between neuronal survival and death during inflammation.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Disease, Cell line
View SamplesGene expression in S2 cells after CG9740 or CP190 RNAi
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Cell line
View SamplesThe approval of genetically modified (GM) crops is preceded by years of intensive research to demonstrate safety to humans and environment. We recently showed that in vitro culture stress is the major factor influencing proteomic differences of GM vs. non-GM plants. This made us question the number of generations needed to erase such memory. We also wondered about the relevance of alterations promoted by transgenesis as compared to environment-induced ones.
Environmental stress is the major cause of transcriptomic and proteomic changes in GM and non-GM plants.
Specimen part
View SamplesPrimary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.
Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.
Specimen part
View SamplesBackground: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids.
Activation of sterol-response element-binding proteins (SREBP) in alveolar type II cells enhances lipogenesis causing pulmonary lipotoxicity.
Specimen part
View SamplesChlamydia trachomatis is an obligate intracellular pathogen that causes trachoma and sextually transmitted disease in human. During early stage of infection, Chlamydia secreted bacterial effector proteins into host cell cytoplasm to help its entry and estabilishment of early replicated niche.
The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling.
Specimen part, Cell line, Time
View SamplesJust as animal monozygotic twins can experience different environmental conditions by being reared apart, individual genetically-identical trees of the genus Populus can also be exposed to contrasting environmental conditions by being grown in different locations. As such, clonally-propagated Populus trees provide an opportunity to interrogate the impact of individual environmental history on current response to environmental stimuli. To test the hypothesis that current responses to an environmental stimulus, drought, are contingent on environmental history, the transcriptome-level drought responses of three economically important hybrid genotypes: DN34 (Populus deltoides x P. nigra); Walker (P. deltoides var. occidentalis x (P. laurifolia x P. nigra)); and, Okanese (Walker x (P. laurifolia x P. nigra)) derived from two different locations were compared. Strikingly, differences in transcript abundance patterns in response to drought were based on differences in geographic origin of clones for two of the three genotypes. This observation was most pronounced for the genotypes with the longest time since establishment and last common propagation. Differences in genome-wide DNA methylation paralleled the transcriptome level trends, where the clones with the most divergent transcriptomes and clone history had the most marked differences in the extent of total DNA methylation, suggesting an epigenetic basis for the clone-history-dependent transcriptome divergence. The data provide insights into the interplay between genotype and environment in the ecologically and economically important Populus genus, with implications for both the industrial application of Populus trees, and the evolution and persistence of these important tree species.
Clone history shapes Populus drought responses.
Specimen part, Treatment
View Samples