New tools for studying microglia in the mouse and human CNS
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Résumé
The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.
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La notice
- Revue
- Proceedings of the National Academy of Sciences
- Thématique
- Neuroinflammation and Neurodegeneration Mechanisms
- Domaine
- Neuroscience
- Établissements canadiens
- —
- Organismes subventionnaires
- National Center for Research ResourcesNational Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Institute on Drug AbuseNational Health and Medical Research CouncilNational Cancer InstituteNational Institutes of HealthNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthDr. Miriam and Sheldon G. Adelson Medical Research FoundationMedical Research CouncilEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentDepartment of Health and Aged Care, Australian GovernmentMyelin Repair FoundationCanadian Institutes of Health Research
- Mots-clés
- MicrogliaBiologyNeuroscienceTransmembrane proteinCell typeAntibodyHuman brainCentral nervous systemCellImmunologyInflammationGeneticsReceptor
- Résumé présent dans OpenAlex
- oui