Secondary microglia formation center in the human fetal brain

Yolk sac-derived microglia migrate and populate the brain during development. The human brain is the largest and most complex brain with the highest cognitive capacity among all species. Therefore, the limitations of rodent brain studies in interpreting the human brain are evident. The microglia in the aggregates lack phagocytic bulbs, membrane ruffles, and long/branching processes compared to microglia in other brain regions. Introducing human microglia into cortical organoids, but not macrophages, replicated proliferative microglial aggregates on the brain organoid surface and sufficiently penetrated deeper regions of the cortical organoids. Penetrating microglia display phagocytic capacity, enhance immunity, and accelerate the maturation of brain organoids. The large proliferative microglial aggregate may be a unique secondary microglial formation center in the human fetal brain to compensate for the enormous microglial demands during brain expansion.