New tools for studying microglia in the mouse and human CNS

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia, the brain's resident immune cells, are crucial for CNS development and disease.
• Distinguishing microglia from other myeloid cells has been challenging due to a lack of specific markers.
• This limitation hinders studies on microglial function in the central nervous system (CNS).

Purpose of the Study:

• To identify a specific marker for microglia to facilitate their study.
• To develop tools for immunostaining, purification, and manipulation of microglia.
• To enable a deeper understanding of microglial roles in the developing, adult, and injured CNS.

Main Methods:

• Identification of Transmembrane protein 119 (Tmem119) as a highly expressed, microglia-specific cell-surface protein in mouse and human.
• Development of monoclonal antibodies targeting Tmem119 for immunostaining and Fluorescence-Activated Cell Sorting (FACS).
• RNA sequencing (RNAseq) of highly pure microglia isolated using Tmem119 antibodies.

Main Results:

• Tmem119 serves as a reliable marker for immunostaining microglia in healthy and diseased brains.
• Pure, nonactivated microglia can be isolated using Tmem119-specific antibodies via FACS.
• RNAseq profiles revealed microglial maturation by the second postnatal week and predicted novel functions.

Conclusions:

• Tmem119 is a valuable microglia-specific marker, enabling precise cellular studies.
• The developed antibodies and RNAseq data provide crucial resources for microglial research.
• These advancements will significantly enhance the understanding of microglia in CNS health and disease.