Somatic mutations reveal the ontogeny of microglia in human aging [snATAC-seq]

In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult hematopoiesis. The origins of human microglia are less clear, but recent evidence suggests that marrow-derived cells contribute to the human microglial pool in certain individuals.

Here, to investigate the ontogeny of human microglia, we develop a method that uses the collection of accumulated somatic mutations which uniquely labels each clone of cells to track the infiltration of marrow-derived cells into the human brain. Applying this method to 20 aged individuals, we find evidence of an influx of marrow-derived cells into the brain in all examined individuals. Single cell analysis, including single cell lineage tracing using mitochondrial DNA variants, demonstrates that these infiltrating cells are similar to microglia and can comprise a large fraction of the microglial pool.