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Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we analyzed the RNA expression patterns of more than 76,000 individual microglia in mice during development, in old age, and after brain injury. Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states-including chemokine-enriched inflammatory microglia-persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human multiple sclerosis lesions. These distinct microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.
Pubmed ID: 30471926 RIS Download
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Publicly available database of the genes, proteins, experimentally-verified interactions and signaling pathways involved in the innate immune response of humans, mice and bovines to microbial infection. The database captures coverage of the innate immunity interactome by integrating known interactions and pathways from major public databases together with manually-curated data into a centralized resource. The database can be mined as a knowledgebase or used with the integrated bioinformatics and visualization tools for the systems level analysis of the innate immune response. Although InnateDB curation focuses on innate immunity-relevant interactions and pathways, it also incorporates detailed annotation on the entire human, mouse and bovine interactomes by integrating data (178,000+ interactions & 3,900+ pathways) from several of the major public interaction and pathway databases. InnateDB also has integrated human, mouse and bovine orthology predictions generated using Ortholgue software. Ortholgue uses a phylogenetic distance-based method to identify possible paralogs in high-throughput orthology predictions. Integrated human and mouse conserved gene order and synteny information has also been determined to provide further support for orthology predictions. InnateDB Capabilities: * View statistics for manually-curated innate immunity relevant molecular interactions. New manually curated interactions are submitted weekly. * Search for genes and proteins of interest. * Search for experimentally-verified molecular interactions by gene/protein name, interaction type, cell type, etc. * Search genes/interactions belonging to 3,900 pathways. * Visualize interactions using an intuitive subcellular localization-based layout in Cerebral. * Upload your own list of genes along with associated gene expression data (from up to 10 experimental conditions) to interactively analyze this data in a molecular interaction network context. Once you have uploaded your data, you will be able to interactively visualize interaction networks with expression data overlaid; carry out Pathway, Gene Ontology and Transcription Factor Binding Site over-representation analyses; construct orthologous interaction networks in other species; and much more. * Access curated interaction data via a dedicated PSICQUIC webservice.
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