Similar Datasets
Project description:Investigate whether miR-155 deletion activates microglia through interferon-dependent mechanism.
2023-04-10 | GSE220304 | GEO
Project description:Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation on the long-term state of the CNS environment has not been characterized. Here, we found by RNA-seq analysis that acute and synchronous microglia depletion results in a type 1-interferon inflammatory signature in degenerating somatosensory cortex in microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type-1 interferon-driven inflammation and restore microglia homeostasis. Together, we found that acute microglia ablation induces a type-1 interferon activation state of grey matter microglia associated with acute neurodegeneration.
2018-06-08 | GSE115447 | GEO
Project description:Microglia repair injury and maintain homeostasis in the brain, but whether aberrant microglial activation can contribute to neurodegeneration remains unclear. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive up-regulation of lysosomal and innate immunity genes, increased complement production, and synaptic pruning activity in microglia. During aging, Grn-/- mice show profound accumulation of microglia and preferential elimination of inhibitory synapses in the ventral thalamus, which contribute to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, blocking complement activation by deleting C1qa gene significantly reduces synaptic pruning by Grn-/- microglia, and mitigates neurodegeneration, behavioral phenotypes and premature mortality in Grn-/- mice. These results uncover a previously unrecognized role of progranulin in suppressing microglia activation during aging, and support the idea that blocking complement activation is a promising therapeutic target for neurodegeneration caused by progranulin deficiency. Gene expression study in multiple brain regions from a mouse model of progranulin deficiency Please note that 9 outlier samples were excluded from data analysis. Therefore, there are 326 raw data columns (i.e. 163 samples) in the non_normalized data matrix while 154 samples are represented here.
2016-03-31 | E-GEOD-75083 | biostudies-arrayexpress
Project description:Purpose: We purified whole brain microglia of MFP2 knockout mice and control mice utilizing percoll gradient and FACS sorting, followed by microarray analysis to define the molecular changes in MFP2 knockout mice at the endstage of the disease. We compared the microglia transcriptome of Mfp2-/- microglia to that of SOD1-G93A microglia isolated from spinal cord to define the microglia signature associated with a non-neurodegenerative environment. Results and conclusions: Mfp2-/- microglia acquire an activation state characterized by activation of mammalian target of rapamycin (mTOR). In addition, activated microglia display reduced expression of genes that are normally highly expressed by surveillant microglia in steady-state conditions. The immunological profile of is heterogeneous and encompasses upregulation of both pro- and anti-inflammatory genes. In contrast to the neurodegeneration-specific microglia profile in SOD1-G93A mice, Mfp2-/- microglia do not induce genes associated with phagocytosis, lysosomal activation and neurotoxicity. 4 MFP2 knockout and 4 control samples were subjected to microarray analysis.
2015-04-14 | E-GEOD-66420 | biostudies-arrayexpress
Project description:To detect total RNA in microglia derived from AD mice (5xFAD) brain we single cell sorted Cd11b+ and Cd45+ cells divided by Methoxy-X04 staining (Ab aggregates) positivity We performed differentially expression analysis of RNA-seq of wild-type microglia (Me-X04 neg), non-phagocytic AD microglia (Me-X04 neg), phagocytic AD microglia (Me-X04 positive)
2024-03-20 | GSE229418 | GEO
Project description:Microglia are brain immune cells that constantly survey their environment to maintain homeostasis. Enhanced microglial reactivity and proliferation are typical hallmarks of neurodegenerative diseases. Whether specific disease-linked microglial subsets exist during the entire course of neurodegeneration, including the recovery phase, is currently unclear. Taking a single-cell RNA-sequencing approach in a susceptibility gene-free model of nerve injury, we identified a microglial subpopulation that upon acute neurodegeneration shares a conserved gene regulatory profile compared to previously reported chronic and destructive neurodegeneration transgenic mouse models. Our data also revealed rapid shifts in gene regulation that defined microglial subsets at peak and resolution of neurodegeneration. Finally, our discovery of a unique transient microglial subpopulation at the onset of recovery may provide novel targets for modulating microglia-mediated restoration of brain health.
2018-08-25 | GSE90975 | GEO
Project description:To detect miRNAs in microglia derived from AD mice (5xFAD) brain we single cell sorted Cd11b+ and Cd45+ cells divided by Methoxy-X04 staining (Ab aggregates) positivity We performed differentially expression analysis of RNA-seq of wild-type microglia (Me-X04 neg), non-phagocytic AD microglia (Me-X04 neg), phagocytic AD microglia (Me-X04 positive)
2024-03-20 | GSE229417 | GEO
Project description:Increasing evidence from recent findings in human samples and animal models support the involvement of inflammation in the development of Parkinson’s disease (PD). Nevertheless, it is currently unknown whether microglia activation could also be a primary event leading to neurodegeneration in PD. We have generated a new mouse model with strictly selective alpha-Synuclein (aSYN) accumulation in microglial cells by inducible gene expression through lentiviral transduction in the nigral tissue. Surprisingly, these mice develop progressive and restricted degeneration of dopaminergic (DA) neurons without any sign of aSYN endogenous aggregation. aSYN accumulating microglial cells exhibit a strong inflammatory status with production of pro-inflammatory cytokines and chemokines. Bulk and scRNA-sequencing of the immune cellular infiltrate identify a complex cellular composition with numerous peripheral populations of the innate and adaptive immune system with specific transcriptional signatures. Molecular profiling and functional assessment reveal that intoxicated microglia develop exhausted phagocytosis and high production of oxidative molecules creating a molecular feed-forward vicious cycle with IFNg secreting immune cells infiltrated in the brain parenchyma. In these animals, pharmacological inhibition of the oxidative and nitrosative molecule production is sufficient to attenuate neurodegeneration. These results suggest that aSYN accumulation in microglia exerts selective DA neuronal degeneration by promoting phagocytic exhaustion, excessive toxic environment and selective recruitment of peripheral immune cells.
2021-09-13 | GSE157533 | GEO
Project description:Purpose: We purified spinal cord microglia utilizing percoll gradients and magnetic beads, followed by transcriptome profiling (RNA-seq) to define microglia expression profiles against other neural, immune cell-types. We next observed how the microglial transcriptomes change during activation in the SOD1-G93A mouse model of motor neuron degeneration at 3 time points. We also compared these profiles with that induced by LPS injection. Results and conclusions: ALS microglia were found to differ substantially from those activated by LPS and from M1/M2 macrophages by comparison with published datasets. These ALS microglia showing substantial induction of a neurodegeneration-tailored phenotype, with induction of lysosomal, RNA splicing, and Alzheimer's disease pathway genes. Overall they express a mixture of neuroprotective and neurotoxic factors during activation in ALS mice, showing that neuro-immune activation in the spinal cord is a double-edged sword. We also detected the transcriptional nature of surface marker expression in microglia (CD11b, CD86, CD11c), and substantial T-cell microglia cross-talk using correlative microglia transcriptome/FACS analysis. 42 total RNA samples from purified spinal cord microglia were subjected to paired-end RNA-sequencing. Parallel flow cytometry data was collected from the same spinal cords.
2013-07-15 | E-GEOD-43366 | biostudies-arrayexpress
Project description:The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-?) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-? bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-?/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-?/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system. polyA RNA profiling of Neural Stem/Progenitor cells (NPCs) cultured in basal/Th1/Th2 conditions, of Exosomes derived from NPCs cultured in basal/Th1/Th2 conditions and of EVs derived from NPCs cultured in Basal/Th1/Th2 conditions. Total RNA was purified using Trizol. Purity and integrity were confirmed by BioAnalyser (Agilent). Paired End library construction and poly-A selection were performed by EASIH (The Eastern Sequence and Informatics Hub, University of Cambridge, Cambridge) according to the Illumina standard protocol. Sequencing was performed by EASIH using Illumina GAII.
2014-09-22 | E-GEOD-33527 | biostudies-arrayexpress