Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. Here, we use this wealth of knowledge as leverage in the design and analysis of a genomic visualization of organizer-related gene transcription. Using ectopic expression of the two major activities of the organizer, BMP and Wnt inhibition, as well as endogenous tissues, we generate a focused set of samples that represent different aspects of organizer signaling. The genomic expression values of each sample are then measured with oligonucleotide arrays. From this data, genes regulated by organizer signaling are selected and then clustered by their patterns of regulation. A new GO biological process annotation of the Xenopus genome allows us to rapidly identify clusters that are highly enriched for known gastrula patterning genes. Within these clusters, we can predict the expression patterns of unknown genes with remarkable accuracy, leading to the discovery of new organizer-related gastrula stage expression patterns for 19 genes. Moreover, the patterns of gene response observed within these clusters allow us to parse apart the contributions of BMP and Wnt inhibition in organizer function. We find that the majority of gastrula patterning genes respond transcriptionally to these activities according to only a few stereotyped patterns, allowing us to describe suites of genes that are likely to share similar regulatory mechanisms. These suites of genes demonstrate a mechanism where BMP inhibition initiates the organizer program before gastrulation, and Wnt inhibition maintains and drives the organizer program during gastrulation.
Genomic analysis of Xenopus organizer function.
Specimen part
View SamplesWe report the effects of exposure to the endocrine disurptor (2-ethylhexyl) phthalate (DEHP) on transcriptome modification in the livers of in vivo Zebrafish. Our data indicate changes in fatty acid metabolism and insulin resistance, pathways associated with the development of Non-Alcoholic Fatty Liver Disease (NAFLD). Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).
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View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex and orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex) from patients with bipolar disorder and matched healthy controls. A cohort of 70 subjects was investigated and the final analysis included 30 bipolar and 31 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls. Orbitofrontal cortex tissue from a cohort of 30 subjects was investigated and the final analysis included 10 bipolar and 11 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View SamplesUMR106-01 osteoblastic cells are a model for studying bone mineralization. We have shown that mineralization is temporally synchronized within cultures grown under defined conditions . Cells are plated at time zero and differentiate into osteoblastic phenotype by 64 h later. If an exogenous phosphate source is added to the cultures, the cells form and deposit hydroxyapatite mineral within distinct extracellular supramolecular lipid protein complexes termed biomineralization foci (BMF) starting 12 h later. Mineralization is largely complete by 24 h later (88 h after plating). We have also shown that AEBSF, covalent serine protease inhibitor, blocks mineralization within BMF and inhibits the fragmentation of several proteins related to biomineralization. The present experiment was designed to test whether AEBSF treatment for 12 h has an effect on transcription by UMR106-01 osteoblastic cells. AEBSF is known to inactivate several serine proteases including SKI-1 (site 1, subtilisin kexin protease-1).SKI-1 functions intracellularly to activate transmembrane bound transcription factor precursors releasing the transcriptionally active N-terminal portions to imported into the nucleus. Thus, if AEBSF blocks transcription of mineralization related genes, it would support a role for SKI-1 in gene regulation in mineralizing UMR106-01 osteoblastic cells.
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Cell line
View SamplesmiR-155 has recently emerged as an important promoter of antitumor immunity through its functions in T lymphocytes. However, the impact of T cell expressed miR-155 on immune cell dynamics in solid tumors remains unclear. In the present study, we used single-cell RNA-sequencing to define the CD45+ immune cell populations within B16F10 murine melanoma tumors growing in either wild-type (WT) or miR-155 T cell conditional knockout (TCKO) mice at different timepoints. miR-155 was required for optimal T cell activation and reinforced the T cell response at the expense of infiltrating myeloid cells. Further, myeloid cells from tumors growing in TCKO mice were defined by an increase in wound healing genes and a decreased IFNg response gene signature. Finally, we found that miR-155 expression predicted a favorable outcome in human melanoma patients and was associated with a strong immune signature. Moreover, gene expression and histological analysis of the Cancer Genome Atlas (TCGA) data revealed that miR-155 expression also correlates with an immune-enriched subtype in 29 other human solid tumor types. Together, our study provides an unprecedented analysis of the cell types and gene expression signatures by immune cells within experimental melanoma tumors and elucidates miR-155's role in coordinating this dynamic response. Overall design: B16F10 murine melanoma cells expressing ovalbumin model antigen were injected subcutaneously (1e6) into wild-type (C57BL/6) and miR-155 T cell conditional knockout mice (n>4). 9 or 12 days after injection, tumors were pooled in each group, and DAPI(-)CD45(+) live tumor infiltrating immune cells were sorted via flow cytometry. Sorted immune cells were processed for single-cell RNA-sequencing via 10x platform.
MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers.
Specimen part, Cell line, Subject, Time
View SamplesWe expressed either only the E7 oncoprotein or the complete early genome region (CER) of the human papillomavirus type 8 in primary human adult skin keratinocytes.
Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis.
Specimen part
View SamplesPurpose: Identify genes and pathways affected in tuft embryos with NTDs Results: Expression of genes associated with neural tube closure and components of non-canonical WNT signaling/PCP pathways were affected Conclusions: TET1 regulates genes associated with neural tube closure Overall design: RNA pooled from the rostrums of E9 (18-22 somites) tuft/tuft embryos with NTD compared with respective wildtype background strain
A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure.
Specimen part, Cell line, Subject
View SamplesSkeletal muscle adapts to exercise training of various modes, intensities and durations with a programmed gene expression response. This study dissects the independent and combined effects of exercise mode, intensity and duration to identify which exercise has the most positive effects on skeletal muscle health. Full details on exercise groups can be found in: Kraus et al Med Sci Sports Exerc. 2001 Oct;33(10):1774-84 and Bateman et al Am J Cardiol. 2011 Sep 15;108(6):838-44.
Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.
Sex, Age, Specimen part, Race, Subject
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