New tools for studying microglia in the mouse and human CNS

TLDR

Microglia are the brain’s resident macrophages involved in development, homeostasis, and disease, but their roles are hard to study because they are difficult to distinguish from related cell types. The study aims to validate Tmem119 as a stable, robust microglial marker in mice and humans. Custom Tmem119 antibodies were used to isolate microglia for deep RNA‑seq, revealing maturation by the second postnatal week in mice. The study provides Tmem119 antibodies, isolation protocols, and RNA‑seq data that show microglia mature by the second postnatal week, enabling deeper insight into their function.

Abstract

Significance Microglia are the tissue resident macrophages of the brain and spinal cord, implicated in important developmental, homeostatic, and disease processes, although our understanding of their roles is complicated by an inability to distinguish microglia from related cell types. Although they share many features with other macrophages, microglia have distinct developmental origins and functions. Here we validate a stable and robustly expressed microglial marker for both mouse and human, transmembrane protein 119 (Tmem119). We use custom-made antibodies against Tmem119 to perform deep RNA sequencing of developing microglia, and demonstrate that microglia mature by the second postnatal week in mice. The antibodies, cell isolation methods, and RNAseq profiles presented here will greatly facilitate our understanding of microglial function in health and disease.