UK DRI at UCL Guest Seminar: Steffen Jung

Monocytes and Brain Macrophages – revisited

Fate mapping studies in animals have shown that microglia, the resident brain macrophages, are established early in embryogenesis. Furthermore, the analysis of adult mice suggested that this cellular compartment also subsequently resists the seeding with cells derived from definitive hematopoiesis. Rather monocyte-derived macrophages (MoMF) fail to efficiently compete with embryo-derived microglia for to-be-defined niches in the brain. Here we will discuss our recent findings that rare MoMF do appear with age in selected brain regions where they retain, despite the prolonged imprint of the tissue environment, distinct expression profiles from microglia. MoMF could thus contribute to age-linked brain pathologies. Indeed, using a chimera system we show that epigenetic alterations resulting from a mutation associated with age-related clonal hematopoiesis, can render these MoMF pathogenic, resulting in neuronal damage and motoric deficits in the recipient animals.