Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1+ microglia

Microglia and border-associated macrophages (BAMs) are critical for brain health, and their dysfunction is associated to disease. Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Here, we demonstrate that monocytes can efficiently replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably to their embryonic counterparts and showed similar longevity. However, monocytes were unable to replicate the distinct identity of embryonically derived BAMs and microglia. Using xenotransplantation, we found that human…

• ER
  European Resuscitation Council

  Award: 101088437 ReplaceMi
• FW
  Fonds Wetenschappelijk Onderzoek

  Awards: OZR3657, G058921N
• NI
  National Institutes of Health

  Award: R01-NS-120960
• HE
  H2020 European Research Council