학술논문

New tools for studying microglia in the mouse and human CNS
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 113(12)
Subject
Biotechnology
Brain Disorders
Neurosciences
2.1 Biological and endogenous factors
1.1 Normal biological development and functioning
Underpinning research
Aetiology
Neurological
Aged
Animals
Antibodies
Monoclonal
Biomarkers
Brain
Cell Division
Cell Lineage
Child
Endotoxemia
Gene Expression Profiling
Gene Expression Regulation
Developmental
Humans
Lipopolysaccharides
Macrophages
Membrane Proteins
Mice
Mice
Knockout
Microglia
Middle Aged
Nerve Crush
Nerve Tissue Proteins
Optic Nerve Injuries
Organ Specificity
Rabbits
Sciatic Nerve
Sequence Analysis
RNA
Temporal Lobe
Transcriptome
microglia
glia
developmental neuroscience
RNAseq
macrophage
Language
Abstract
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.