Embryonic primitive macrophages colonize the brain where they differentiate into microglia. Microglia were shown to contribute to brain development in animal models but their roles in human brain development remain poorly understood due to the lack of tissue access. The generation of brain organoids from induced human pluripotent stem cells (iPSCs) has been shown to recapitulate the human embryonic brain development process. However, such organoids lack microglia. Here, we generated microglia-sufficient brain organoids by co-culturing brain organoids and primitive-like macrophages (iMacs) generated from the same human iPSCs. We showed that the iMacs contain a high level of lipid droplets and modulate the metabolism, proliferation and axon development of neuronal progenitor cell (NPC) in the organoids. The lipid droplets-loaded macrophages were also observed in mouse and human embryonic brain. Microglia-sufficient brain organoid may help us to gain insights into the functions of microglia during early stage of human brain development.
Macrophage, Microglia, Brain organoid, iPSC, NPC, iMac
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