Expression data from the spinal cord of dmy rat with Mrs2 mutation
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE88855 | GEO | 2016/10/19
SECONDARY ACCESSION(S): PRJNA348812
REPOSITORIES: GEO
Similar Datasets
Project description:Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4+ and CD8+ T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.
2020-07-27 | GSE127319 | GEO
Project description:Magnesium is essential for cellular life, but how it is homeostatically controlled still remains poorly understood. Here we report that members of CNNM family, which have been controversially implicated in both cellular Mg2+ influx and efflux, selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. Co-expression of CNNMs with the channel markedly increased uptake of divalent cations, which is prevented by an inactivating mutation to the channel’s pore. Knockout of Trpm7 in cells or application of the TRPM7-channel inhibitor NS8593 also interfered with CNNM-stimulated divalent cation uptake. Conversely, knockout of CNNM3 and CNNM4 in HEK-293 cells significantly reduced TRPM7-mediated divalent cation entry, without affecting TRPM7 protein expression or its cell surface levels. Furthermore, we found that cellular overexpression of Phosphatases of Regenerating Liver (PRLs), a known CNNMs binding partner, stimulated TRPM7-dependent divalent cation entry and that CNNMs were required for this activity. Whole-cell electrophysiological recordings demonstrated that deletion of CNNM3 and CNNM4 from HEK-293 cells interfered with heterologously expressed and native TRPM7 channel function. We conclude that CNNMs employ the TRPM7 channel to mediate divalent cation influx and that CNNMs also possess separate TRPM7-independent Mg2+ efflux activities that contribute to CNNMs’ control of cellular Mg2+ homeostasis.
2021-11-15 | PXD026635 | Pride
Project description:In many Gram-negative bacteria, the stress sigma factor of RNA polymerase, σS/RpoS, remodels global gene expression to reshape the physiology of quiescent cells and ensure their survival under non-optimal growth conditions. In the foodborne pathogen Salmonella enterica serovar Typhimurium, σS is also required for biofilm formation and virulence. We have recently shown that a ΔrpoS mutation affects the magnesium content of Salmonella and expression of the primary Mg2+-transporter CorA. The other two Mg2+-transporters of Salmonella are encoded by the PhoP-activated mgtA and mgtB genes expressed under magnesium starvation, whereas the corA gene is expressed constitutively. The σS control of corA prompted us to evaluate the impact CorA in quiescent Salmonella cells, by using global and analytical proteomic analyses and physiological assays. The ΔcorA mutation conferred a competitive disadvantage to exit from stationary phase, and slightly impaired motility, but had no effect on total and free cellular magnesium contents. In contrast to the wild type strain, the ΔcorA mutant produced MgtA, but not MgtB, in the presence of high extracellular magnesium concentration. Under these conditions, MgtA production in the ΔcorA mutant did not require PhoP and, consistently, a ΔmgtA, but not a ΔphoP, mutation slightly reduced the magnesium content of the ΔcorA mutant. Nevertheless, the ΔphoP mutation strongly impaired growth and motility, in the absence of CorA only and independently of the extracellular magnesium concentration, unraveling the importance of PhoP-dependent functions in the absence of CorA. Under these conditions, several proteins involved in flagella formation, chemotaxis and secretion were affected by the ΔcorA and ΔphoP mutations in combination, but not alone. Altogether, our data pinpoint a regulatory network, where the absence of CorA is sensed and its physiological consequences alleviated by induction of MgtA- and PhoP- dependent compensatory mechanisms.
2023-10-24 | PXD041489 | Pride
Project description:The distal convoluted tubule (DCT) plays a key role in the fine-tuning of renal Mg2+ reabsorption. In recent years, hereditary magnesium (Mg2+) transport disorders have helped to identify important players in DCT Mg2+ homeostasis. Here, we report the Mg2+-sensitive transcriptional expression of the DCT transcriptome using gene expression microarray analysis. Mice expressing eGFP under a DCT-specific promoter were subjected to Mg2+-deficient or Mg2+-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter (COPAS) allowed isolation of eGFP-positive DCT cells. RNA extracts were subjected to pair-wise microarray analysis, high vs. low Mg2+. Of all genes in the genome, 46 were shown to be differentially expressed with a minimal fold-change of 2. Several known magnesiotropic genes, such as Trpm6 and Parvalbumin, were upregulated in the low Mg2+ fraction. Moreover, new genes were identified that are potentially involved in renal Mg2+ homeostasis. To confirm that the selected candidate genes are regulated by dietary Mg2+ availability, the expression levels of Slc41a3, Pcbd1, Tbc1d4 and Umod were determined by RT-PCR analysis. Indeed, all four genes were shown to be significantly upregulated in mice fed the Mg2+-deficient diet. In conclusion, by elucidating the Mg2+-sensitive DCT transcriptome, new candidate players in renal Mg2+ homeostasis were identified. RNA samples were isolated from PV-eGFP-positive tubules from mice fed on a low (L-samples) or high (H-samples) magnesium diet. Littermate H and L samples were labeled and put on mouse microarrays together. Two of the four sample sets were analyzed in dye-swap to compensate for dye-biases.
2013-12-13 | E-GEOD-40208 | biostudies-arrayexpress
Project description:M. tuberculosis membrane protein PerM is required for persistence in chronic mouse infection. In vitro, the perM mutant requires increased magnesium for replication and survival, with elongation and lysis in low-magnesium media. To gain insight into the function of PerM, we compared the transcriptomes of wt and perM mutant Mtb grown in high (2000 μM) and reduced (250 μM) Mg2+ in three independent experiments. Transcriptome analysis of the perM mutant grown in reduced magnesium revealed upregulation of cell division and cell wall biosynthesis genes.
2015-01-05 | GSE57263 | GEO
Project description:The distal convoluted tubule (DCT) plays a key role in the fine-tuning of renal Mg2+ reabsorption. In recent years, hereditary magnesium (Mg2+) transport disorders have helped to identify important players in DCT Mg2+ homeostasis. Here, we report the Mg2+-sensitive transcriptional expression of the DCT transcriptome using gene expression microarray analysis. Mice expressing eGFP under a DCT-specific promoter were subjected to Mg2+-deficient or Mg2+-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter (COPAS) allowed isolation of eGFP-positive DCT cells. RNA extracts were subjected to pair-wise microarray analysis, high vs. low Mg2+. Of all genes in the genome, 46 were shown to be differentially expressed with a minimal fold-change of 2. Several known magnesiotropic genes, such as Trpm6 and Parvalbumin, were upregulated in the low Mg2+ fraction. Moreover, new genes were identified that are potentially involved in renal Mg2+ homeostasis. To confirm that the selected candidate genes are regulated by dietary Mg2+ availability, the expression levels of Slc41a3, Pcbd1, Tbc1d4 and Umod were determined by RT-PCR analysis. Indeed, all four genes were shown to be significantly upregulated in mice fed the Mg2+-deficient diet. In conclusion, by elucidating the Mg2+-sensitive DCT transcriptome, new candidate players in renal Mg2+ homeostasis were identified.
2013-12-13 | GSE40208 | GEO
Project description:In our previous work, we showed the positive effect of the magnesium and the negative effect of the copper on yeast fermentation performance. The magnesium increases the ethanol yield and a faster glucose consumption by the yeast, on the other hand, the copper provides an opposite effect in yeast under fermentation condition. Therefore, from this contrasting effect we performed the gene-wide expression analysis in the industrial yeast Saccharomyces cerevisiae JP1 under fermentation condition in order to reveal the gene expression profile upon magnesium and copper supplementation. Fermentation assays was performed with the industrial yeast S. cerevisiae JP1 in reference medium (mineral concentration balanced), in the medium supplemented with 500 mg/L of magnesium (Mg2+ medium) and in the medium supplemented with 1 mg/L of copper (Cu2+ medium).
2015-12-09 | E-GEOD-75803 | biostudies-arrayexpress
Project description:M. tuberculosis membrane protein PerM is required for persistence in chronic mouse infection. In vitro, the perM mutant requires increased magnesium for replication and survival, with elongation and lysis in low-magnesium media. To gain insight into the function of PerM, we compared the transcriptomes of wt and perM mutant Mtb grown in high (2000 M-NM-<M) and reduced (250 M-NM-<M) Mg2+ in three independent experiments. Transcriptome analysis of the perM mutant grown in reduced magnesium revealed upregulation of cell division and cell wall biosynthesis genes. Bacteria were grown for 5 days in SautonM-bM-^@M-^Ys media containing 250 or 2000 M-NM-<M MgCl2 and 0.05% Tween 80. Three independent experiments were performed.
2015-01-05 | E-GEOD-57263 | biostudies-arrayexpress
Project description:Alzheimer’s disease (AD) is the most common form of dementia and neurodegenerative disease with increasing prevalence due to longer lifespan in the human population. Why aging constitutes the greatest risk factor for development of AD, however, remains poorly understood. Aging markedly affects oligodendrocytes and the structural integrity of their myelin sheaths which also causes secondary tissue inflammation. We propose a mechanistic link between aging-associated myelin dysfunction and the deposition of Amyloid-ß (Aß) as primary neuropathological hallmark of early AD and hypothesized that breakdown of myelin - especially in cortical regions – is an upstream driver of amyloid deposition in AD. Here, we show that in transgenic mouse models of AD, genetically induced myelin defects by Cnp or Plp1 depletion, as well as direct demyelination are potent drivers of amyloid deposition in vivo as shown by light sheet microscopy imaging. At transcriptomic level, bulk and single-cell RNA sequencing revealed successfully induced disease-associated-microglia (DAM)-like phenotypes in Cnp-/- animals. These activated microglia, however, are primarily engaged with myelin seemingly preventing the protective reactions of the microglia pool to Aß plaques. Our work, therefore, identifies myelin aging as a previously overlooked risk factor for AD and makes the case for myelin health-directed therapies in AD.
2023-03-20 | GSE178296 | GEO
Project description:To learn about the cellular processes involved in Mg2+ transport and the mechanisms allowing cells to cope with low Mg2+ availability, we performed RNA expression profiling experiments, and followed changes in gene activity upon Mg2+ depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg2+ depletion is also induced by high Ca2+ and/or alkalinization. Among the genes significantly up-regulated by Mg2+ starvation, Ca2+ stress and alkalinization are ENA1 (encoding a P-type ATPase sodium pump) and PHO89 (encoding a sodium/phosphate cotransporter). We show that up-regulation of these genes is dependent on the calcineurin/Crz1p signaling pathway. Similarly to Ca2+ stress, Mg2+ starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon Mg2+ starvation depends on extracellular Ca2+. Using fluorescence resonance energy transfer microscopy we demonstrate that removal of Mg2+ results in an immediate increase in free cytoplasmic Ca2+. This effect is dependent on external Ca2+. Results presented indicate that Mg2+ depletion in yeast cells leads to enhanced cellular Ca2+ concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg2+ depletion stress. Keywords: stress response (magnesium starvation)
2007-03-08 | GSE6687 | GEO