We performed RNA-seq to profile gene expression in the heads and whole bodies of 32 isofemale fly lines from two divergent microclimates at ''Evolution Canyon'' in Israel (16 fly lines from each microclimate). We also measured RNA editing levels in the head tissue of these flies. Overall design: For each of the 32 isofemale fly lines from ''Evolution Canyon'', gene expression profiles of whole bodies and heads, along with RNA editing profiles of heads of 3-5 day old male flies through RNA-seq.
Regulation of gene expression and RNA editing in Drosophila adapting to divergent microclimates.
Specimen part, Subject
View SamplesHepG2 and THP-1 cells, the latter differentiated by phorbol 12-myristate 13-acetate (PMA), were co-cultured and characterized for typical liver-specific functions, such as xenobiotic detoxification, lipid and cholesterol metabolism. Furthermore, liver injury-associated pathways, such as inflammation, were studied. In general, the co-cultivation of these cells produced a pro-inflammatory system, as indicated by increased levels of cytokines (IL-8, TGF-α, IL-6, GM-CSF, G-CSF, TGF-β, and hFGF) in the respective supernatant. Increased expression levels of target genes of the aryl hydrocarbon receptor (AHR), e.g., CYP1A1, CYP1A2 and CYP1B1, were detected, accompanied by the increased enzyme activity of CYP1A1. Moreover, transcriptome analyses indicated a significant upregulation of cholesterol biosynthesis, which could be reduced to baseline levels by lovastatin. In contrast, total de novo lipid synthesis was reduced in co-cultured HepG2 cells. Key events of the adverse outcome pathway (AOP) for fibrosis were activated by the co-cultivation, however, no increase in the concentration of extracellular collagen was detected. This indicates, that AOP should be used with care. In summary, the indirect co-culture of HepG2/THP 1 cells results in an increased release of pro-inflammatory cytokines, an activation of the AHR pathway and an increased enzymatic CYP1A activity.
Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.
Treatment
View SamplesKlotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies.
The anti-aging and tumor suppressor protein Klotho enhances differentiation of a human oligodendrocytic hybrid cell line.
Specimen part, Cell line, Treatment
View SamplesOur study demonstrated that e-cigarettes, both with and without nicotine, induced sex-dependent gene expression change. This RNA-seq study examined the expression profiles of brain frontal cortex samples from mice exposed to classic tobacco flavored bluâ„¢ e-cigarettes during gestation and lactation. Overall design: Brains were extracted and sectioned from ~1-month-old male and female offspring the week following exposure, RNA was isolated and purified from frontal cotrex tissues, and gene expression profiles were analyzed by RNA Sequencing.
Microglia Activation and Gene Expression Alteration of Neurotrophins in the Hippocampus Following Early-Life Exposure to E-Cigarette Aerosols in a Murine Model.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease.
Treatment
View SamplesScope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease.
No sample metadata fields
View SamplesPKA activation by FSH is essential to transduce FSH-mediated effects on granulosa cell proliferation, differentiation and steroidogenesis. However, It is unknown whether activation of PKA is sufficient to account for the entire program of granulosa cell responses to FSH. We addressed this question by conducting a comprehensive comparative analysis of signaling pathways and gene expression profiles of granulosa cells stimulated with FSH or expressing a constitutively active PKA mutant, PKA-CQR.
Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation.
Age, Specimen part, Treatment
View SamplesBecause most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions.
Transcriptomics of post-stroke angiogenesis in the aged brain.
Sex, Age, Specimen part
View SamplesMating triggers physiological and behavioral changes in females.
Mating induces an immune response and developmental switch in the Drosophila oviduct.
No sample metadata fields
View SamplesScope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease.
Treatment
View Samples