In this study, we explored the diverse macrophage populations in the brain, including parenchymal microglia, border-associated macrophages, and monocyte-derived cells, all of which are crucial for brain development and maintaining homeostasis. These populations also play roles in aging and neurodegenerative diseases. However, their specific phenotypes, functions, and locations in various contexts remain unclear. We generated a murine brain myeloid single-cell RNA sequencing (scRNA-seq) integration to map these populations systematically. We found that the disease-associated microglia (DAM) population, previously identified in Alzheimer's disease models, consists of two distinct cell lineages: TREM2-dependent, embryonically derived DAM that express a neuroprotective signature, and monocyte-derived, TREM2-expressing disease-inflammatory macrophages (DIMs) that accumulate in the
brain with aging. These two populations are also conserved in the human brain. Our work provides an ontogeny-resolved model of brain myeloid cell diversity, shedding light on their roles in development, homeostasis, and disease, and identifies potential cellular targets for treating neurodegeneration.
DOI: 10.1016/j.immuni.2022.07.004
