The goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.
A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.
Subject
View SamplesCancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Specimen part
View SamplesAdult mouse gene expression patterns in common strains
Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice.
No sample metadata fields
View SamplesIdentification of transcriptional profiles stimulated by the complement protein C1q in rat immature neurons associated with the C1q-dependent neuroprotection observed in vitro.
Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression.
Specimen part
View SamplesMultiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow in order to survive and proliferate. Interactions between the malignant plasma cell and bone marrow mesenchymal stem cell (BMMSC) are thought to be a critical determinant of this requirement, and include both physical and chemical components. There is increasing evidence that the phenotype of the BMMSC is stably altered in patients with MM. More recently, it has been suggested that this phenotypic transformation is also observed in patients with the benign condition known as monoclonal gammopathy of undetermined significance (MGUS), which almost always precedes MM. In this study, we describe a mechanism by which the peptidyl arginine deiminase 2 (PADI2) enzyme plays an key role in the control of malignant plasma cell phenotype by BMMSCs. PADI enzymes deiminate (citrullinate) peptidyl arginine residues, changing the function or interactions made by the target protein. We identified PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through citrullination of arginine residue 26 of histone H3, it induces the upregulation of interleukin-6 (IL-6) expression. This directly leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.
Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesIn this study, we developed a unique system using primary human autologous lymphocytes and HMDMs to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. Our results showed that C1q bound to autologous apoptotic lymphocytes (AL) significantly modulated the response of HMDMs to LPS by increasing expression of cytokines, chemokines and effector molecules associated with immunoregulation and by directly suppressing caspase-1 dependent cleavage of IL-1beta.
Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.
No sample metadata fields
View SamplesComplement protein C1q is induced after injury in the brain and during Alzheimer's disease and has been shown to protect against amyloid-beta induced neuronal death. In this study, we used microarray approach to identify the pathways modulated by C1q that are associated with neuroprotection.
C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-β neurotoxicity.
Specimen part, Treatment
View SamplesThe motor neurons innervating the muscles of facial expression are organized into somatotopic hindbrain clusters termed subnuclei. Each of the medial, intermediate, dorsolateral, and lateral subnuclei gives rise to a specific branch of the facial motor nerve (cranial nerve VII). How subnucleus-specific gene expression could mediate the accurate development of facial nerve projections was not well understood.
Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development.
Sex, Specimen part
View SamplesC5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways. Overall design: Microglia mRNA profiles of wildtype (WT), C5aR1 knockout (C5aR1KO), Arctic (ARC) and Arctic C5aR1 knockout (ARCKO) mice at 2, 5, 7 and 10-11 month. Duplicates were sequenced for each genotype on Illumina HiSeq 2500 platform.
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Age, Specimen part, Subject
View SamplesStudies of gene expression profiles using the whole genome wide microarray analysis in SUM149PT cells (ER-, p53mut) and SUM190PT cells (ER-, p53mut) when treated with 5 or 7.5 M CG-1521 alone and in combination with 10 nM 17-Estradiol. Comparisons between each treatment group provides evidence for the dysregulation of genes associated with the spindle assembly checkpoint.
Histone deacetylase inhibitors modulate miRNA and mRNA expression, block metaphase, and induce apoptosis in inflammatory breast cancer cells.
Cell line
View Samples