Purpose: Aim of the study is to identify functional differences between the P1 and P2-HNF4a isoforms. To do this, we generated Tet-On inducible lines that express either the human (P1) HNF4a2 or (P2) HNF4a8 under control of DOX in the HCT116 human colon cancer cells. Methods: HNF4a2 and Parental lines were induced with 0.3 µg/mL DOX, while HNF4a8 line was induced with either 0.1 or 0.3 µg/mL DOX for 24 hours. Samples were generated by deep sequencing, using the Illumina TruSeq RNA. Result: There were common and unique dysregulated genes identified in the HNF4a2 and HNF4a8 lines (+DOX); more upregulated genes than downregulated genes in both the lines. Conclusion: The functional difference between HNF4a2 and HNF4a8 is that the latter tends to upregulate genes involved in proliferation and anti-apoptosis while HNF4a2 upregulates genes involved in growth suppression and cell death. Overall design: Tet-On inducible HCT116 cell (Parental, HNF4a2, and HNF4a8) lines, treated with (0.0, 0.1, or 0.3 µg/mL) DOX for 24 hours, were 50bp pair-ended sequenced in triplicate using Illumina TruSeq RNA Sample Prep v2 Kit.
Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.
No sample metadata fields
View SamplesThe mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH.
Molecular interplay between Δ5/Δ6 desaturases and long-chain fatty acids in the pathogenesis of non-alcoholic steatohepatitis.
Specimen part, Disease, Disease stage
View SamplesActivation of the innate immune system leading to a persistent state of low-grade of tissue inflammation greatly influences the risk of developing metabolic complications associated with obesity. In this study, we characterized the inflammatory state in adipose tissue from obese patients and explored the potential of the specialized pro-resolving mediator (SPM) resolvin D1 (RvD1) to actively terminate inflammation and promote its resolution. By means of high-troughput transcritomic analysis we identified a cytokine-related molecular signature in obese omental adipose tissue, characterized by a remarkable overexpression of interleukin (IL)-6, IL-1 and IL-10 associated with a concomitant increase in macrophage infiltration, which gradually increased in a body mass index-dependent manner.
Signaling and Immunoresolving Actions of Resolvin D1 in Inflamed Human Visceral Adipose Tissue.
Specimen part, Disease stage
View SamplesWe access the activity-dependent genes in olfactory neuron cells with unilateral naris occlusion model with mouse. Overall design: mRNA profile of olfactory epithelia between closed and open sides of mice naris was compared
Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.
Specimen part, Cell line, Subject
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. This series describes 1 of the 5 array experiments.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View SamplesConditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency.
Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.
Specimen part
View Samples