EGFR and MEK pathways were activated alone or in combination in human mammary epithelial cells. We profiled the pathway gene expression signatures using RNA-Seq. Overall design: mRNA was extracted from human mammary epithelial cells overexpressing EGFR gene, MEK gene, or EGFR and MEK genes in combination (or GFP control) for RNA-Seq analysis. Experiment was performed in six replicates per condition.
ASSIGN: context-specific genomic profiling of multiple heterogeneous biological pathways.
No sample metadata fields
View SamplesAberrant TGFbeta signalling is a hallmark of epithelial derived tumours. Signalling patterns can depend on the membrane trafficking and internalization of the TGFbeta receptors. Protein kinase C (PKC), particularly the atypical PKC isoforms, alter the trafficking of TGFbeta receptors and can alter TGFbeta induced gene expression.
aPKC alters the TGFβ response in NSCLC cells through both Smad-dependent and Smad-independent pathways.
Cell line, Treatment, Time
View SamplesThe pancreatic beta cells are the only cells that can produce insulin in response to prevailing glycemia. The development of beta cells was found to be depending on the activity of a complex genetic network. Overexpression of transcriptional factor MafK in beta cells have resulted in impairment of thier functions and suppressed insulin secretion and increased the severity of beta cell loss resulting in an overt diabetes.
β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.
Specimen part
View SamplesThe goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.
Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.
No sample metadata fields
View SamplesWe conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Effects of moderate drinking during pregnancy on placental gene expression.
Specimen part
View SamplesMacrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and alterations in mRNA levels were analyzed. We identified three transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands, in the presence of three different “reprogramming” signals; high density immune complexes (IC), prostaglandin E2 (PGE2), or adenosine (Ado). All three of these cell populations produced higher levels of transcripts for IL-10, and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1Beta, IL-6, and IL-12. All three macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore we consider each to have immunoregulatory activity. This immunoregulatory activity occurred equally well in macrophages from stat6-deficient mice. The lack of STAT6 did not affect macrophages’ ability to reciprocally change cytokine production or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These immunoregulatory macrophages are transcriptionally and functionally related, and quite distinct from macrophages treated with IL-4.
The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.
No sample metadata fields
View SamplesCirculating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape of circulating RNA in human subjects. By focusing on tissue-specific genes, we were able to identify the relative contributions of these tissues to circulating RNA and monitor changes during tissue development and neurodegenerative disease states.
Noninvasive in vivo monitoring of tissue-specific global gene expression in humans.
No sample metadata fields
View SamplesCirculating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We employed high throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA, and to monitor changes in tissue development and health.
Noninvasive in vivo monitoring of tissue-specific global gene expression in humans.
Specimen part
View SamplesPlasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN- in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity
Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity.
Sex, Specimen part
View SamplesThe goal of this study is to simultaneously examine host and parasite gene expression programs in skin lesions of human patients infected with the intracellular parasite Leishmania. We conducted high-resolution sequencing of the transcriptomes from early and late stage cutaneous leishmaniasis biopsies using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes, helping to explain tuning of the immune response to parasite transcriptomic profiles present in the lesion microenvironment. This data provided a deeper look at the transcriptomic profile of the host response in conjunction with a novel look at the parasite transcriptome in human cutaneous lesions. These data also offer the first glimpse of Leishmania gene expression profiles specific to the cutaneous manifestation of disease in human patients. This metatranscriptomic study provides a solid framework for future functional, genomic, and clinical studies of leishmaniasis as well as intracellular pathogenesis in general.
Meta-transcriptome Profiling of the Human-Leishmania braziliensis Cutaneous Lesion.
No sample metadata fields
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