Transcription profiling by array of mouse male retinas to investigate IGF-I-induced chronic gliosis and retinal stress
Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy.
Sex, Specimen part
View SamplesLack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment against non-alcoholic steatohepatitis (NASH) progression and/or regression of nonalcoholic fatty liver disease (NAFLD). Nitro-oleic acid (OA-NO2) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was studied in a model of long-term NASH diet-induced liver damage. Non-invasive imaging (e.g. photoacustic-ultrasound (PA-US)) was pursued to establish advanced experimental NASH in mice in which both steatosis and fibrosis were diagnosed prior experimental OA-NO2 therapy. CLAMS and NMR-based analysis demonstrates that OA-NO2 improves body composition and energy metabolism and inhibits hepatic triglyceride accumulation. PA-US imaging revealed a robust inhibition of liver steatosis and fibrosis by OA-NO2. RNA-sequencing analysis uncovered inflammation and fibrosis as major pathways suppressed by OA-NO2 administration, as well as regulation of lipogenesis and lipolysis pathways, with a robust inhibition of SREBP1-dependent lipogenic gene expression by OA-NO2. Global liver transcriptome in response to OA-NO2 was confirmed in vivo and in isolated hepatocytes. These results were further supported by histological analysis and quantification of lipid accumulation, lobular inflammation (F4/80 staining) and fibrosis (collagen deposition, aSMA staining) as well as established parameters of liver damage (ALT). In vitro studies indicate that OA-NO2 inhibits TG biosynthesis and accumulation in hepatocytes and inhibits fibrogenesis in human stellate cells. Taken together, OA-NO2 improve steatohepatitis and fibrosis and may constitute an effective therapeutic approach against advanced NAFLD that warrants further clinical evaluation. Overall design: C57BL/6J mice were fed standard chow diet (CD) or NASH-diet rich in saturated fat, trans-fat, fructose and cholesterol (40% of calories from fat, Research Diets D17010103) for 24 weeks. All mice were maintained on a 12-hour light/dark cycle and had ad libitum access to food and water. Mice were subjected to subcutaneous implantation of osmotic minipumps for delivery of polyethylenglycol (PEG), PEG-solvated oleic acid (OA), or PEG-solvated OA-NO2 at an infusion rate of 5 mg/kg/day.
Nitro-fatty acids protect against steatosis and fibrosis during development of nonalcoholic fatty liver disease in mice.
Specimen part, Cell line, Subject
View SamplesDouble-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood. Here we show that human Staufen1-containing complexes contain essential elements of the gene silencing apparatus, like Ago1-3 proteins, and we describe a set of miRNAs specifically associated to complexes containing human Staufen1. Among these, miR124 stands out as particularly relevant because it appears enriched in human Staufen1 complexes and is over-expressed upon differentiation of human neuroblastoma cells in vitro. In agreement with these findings, we show that expression of human Staufen1 is essential for proper dendritic arborisation during neuroblastoma cell differentiation, yet it is not necessary for maintenance of the differentiated state, and suggest potential human Staufen1 mRNA targets involved in this process.
Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation.
Cell line
View SamplesThe transcriptional data from an integrative analysis of transcriptional and metabolic stress responses that provides a more complete understanding of the mechanisms by which genetic regulatory circuits mediate metabolic phenotype.
Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p.
No sample metadata fields
View SamplesTo ask whether MANF contributes to the rejuvenating effects of heterochronic parabiosis, we generated heterochronic pairs in which 20 month old WT mice were combined with either 4 month old MANFHet (O-YgHet) or WT (O-YgWT) littermates, and maintained for 5 weeks before analysis. Control pairs in which old WT mice were combined together (O-O) were used. Livers were collected from each animal in the pair and RNA was sequenced for 5 independent animals/condition. Overall design: RNA was extracted and sequenced for 5 animals/condition
MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage.
Age, Subject
View SamplesIn the nervous system, neural stem cells (NSC) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3-/- mice have fewer NSC in vivo than wild type counterparts. NSC isolated from adult FoxO3-/- mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSC suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSC might have important implications for counteracting brain aging in long-lived species.
FoxO3 regulates neural stem cell homeostasis.
Specimen part
View SamplesThe biotrophic fungus Ustilago maydis causes smut disease on maize (Zea mays L.), which is characterized by immense plant tumours. To establish disease and reprogram organ primordia to tumours, U. maydis deploys effector proteins in an organ-specific manner. However, the cellular contribution to leaf tumours remains unknown. We investigated leaf tumour formation on the tissue- and cell type-specific level. Cytology and metabolite analysis were deployed to understand the cellular basis for tumourigenesis. Laser-capture microdissection was performed to gain a cell-type specific transcriptome of U. maydis during tumour formation. In-vivo visualization of plant DNA synthesis identified bundle sheath cells as the origin of hyperplasic tumour cells, while mesophyll cells become hypertrophic tumour cells. Cell type specific transcriptome profiling of U. maydis revealed tailored expression of fungal effector genes. Moreover, U. maydis See1 was identified the first cell type specific fungal effector, being required for induction of cell cycle reactivation in bundle sheath cells. Identification of distinct cellular mechanisms in two different leave cell types, and See1 as an effector for induction of proliferation of bundle-sheath cells, are major steps in understanding U. maydis-induced tumor formation. Moreover, the cell-type specific U. maydis transcriptome data is a valuable resource to the scientific community. Overall design: To analyze the cell type specific transcriptome of U. maydis during the indcution of plant tumors, transcriptomic profiling of U. maydis from LCM-dissected tumour cells was done. At 4 dpi, SG200 infected HTT cells, bundle sheath-derived HPT cells, and SG200?see1 infected HTT cells (?see1 HTT) were isolated. As controls, mesophyll and bundle sheath cells from mock treated leaf tissue of the same age were isolated.
Cell type specific transcriptional reprogramming of maize leaves during Ustilago maydis induced tumor formation.
Specimen part, Subject
View SamplesTissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment.
The molecular signature of tissue resident memory CD8 T cells isolated from the brain.
Specimen part
View SamplesWild type, pkl, pkr2 and pkl pkr2 plants were grown, and gene expression in roots was compared at the age of 5 days. <br></br>
CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis.
None
Age, Specimen part, Time
View SamplesThe putative trancriptional regulator PA2449 was found to be essential for both glycine/serine metabolism and the production of phenazines in P. aeruignosa PAO1.
Gene PA2449 is essential for glycine metabolism and pyocyanin biosynthesis in Pseudomonas aeruginosa PAO1.
No sample metadata fields
View Samples