we performed RNAseq between WT/KO and WT/C99F to understand the function of PHF6 in gene regulation Overall design: RNAseq for WT, KO and C99F cortex at p0
Characterization of a Mouse Model of Börjeson-Forssman-Lehmann Syndrome.
Specimen part, Cell line, Subject
View SamplesMitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process, and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative datasets that can be leveraged to explore post-transcriptional and post-translational processes that are essential for mitochondrial adaptation.
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Cell line, Treatment
View SamplesThe therapeutic potential of pro-resolution factors in determining the outcome of inflammatory events has gained ground over the past decade. However, the attention has been focused on the non-genomic effects of these endogenous, anti-inflammatory substances. In this study, we have focused our attention on identifying specific annexin 1 (AnxA1) protein/ALX receptor mediated gene activation, in an effort to identify down-stream genomic targets of this well-known, glucocorticoid induced, pro-resolution factor.
Downstream gene activation of the receptor ALX by the agonist annexin A1.
No sample metadata fields
View SamplesMalignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions.
Melanomas prevent endothelial cell death under restrictive culture conditions by signaling through AKT and p38 MAPK/ ERK-1/2 cascades.
Specimen part
View SamplesComplement inhibitor C4b-binding protein (C4BP) is synthesized in liver and pancreas and composed of 7 identical alpha chains and one unique beta chain. We showed previously that C4BP binds islet amyloid polypeptide (IAPP) and affects fibril formation in vitro. Now we found that polymeric C4BP inhibited lysis of human erythrocytes incubated with monomeric IAPP while no erythrocyte lysis was observed after incubation with preformed IAPP fibrils. In contrast, monomeric alpha chain of C4BP had significantly reduced activity. Further, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in decreased cell viability, which was restored in the presence of physiological concentrations of C4BP. Accordingly, addition of C4BP rescued the ability of INS-1 cells and isolated rat islets to respond to glucose stimulation with insulin secretion, which was impaired in the presence of IAPP alone. C4BP was internalized together with IAPP into INS-1 cells and therefore we aimed to study its effect on gene expression. Pathway analyses of mRNA expression microarray data indicated that cells exposed to C4BP and IAPP in comparison to IAPP alone increased expression of genes involved in cholesterol synthesis. Depletion of cholesterol through methyl--cyclodextrin or cholesterol oxidase abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells. Also, inhibition of phosphoinositide 3-kinase but not NF-B had a similar effect. Taken together, one of the mechanisms by which C4BP protects beta-cells from IAPP cytotoxicity is by enhancing cholesterol synthesis.
C4b-binding Protein Protects β-Cells from Islet Amyloid Polypeptide-induced Cytotoxicity.
Specimen part, Cell line
View SamplesBackground and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1 and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism.
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion.
Sex, Specimen part, Disease
View SamplesIn the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation.
Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole.
No sample metadata fields
View SamplesThe goals were to investigate differences in gene expression between wild type and Gpr120 knockout mouse interscapular brown adipose tissue
The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sex, Specimen part
View SamplesGenome wide expression analysis of 92 adult and 14 fetal liver samples
Genetic and epigenetic regulation of gene expression in fetal and adult human livers.
Sex, Specimen part
View Samples