We have discovered that the adult CNS has a remarkable capacity to regulate its microglial population. Using CSF1R inhibitors we are able to deplete the adult brain of >95% of all microglia. Withdrawal of inhibitor results in the rapid repopulation of the entire CNS, with new cells appearing within just 3 days. These new cells differentiate into new microglia over the course of the next 7-14 days, resulting in a fully repopulated animal.
These repopulating microglia derive from cells that are induced to proliferate in response to 1) microglial depletion and 2) CSF1R inhibitor withdrawal. They are resident in the CNS, found ubiquitously throughout the brain, and initially express nestin, a neuroectodermal marker. Within 24 hours they express microglial markers, including CX3CR1, AIF1, SIGLECH, TMEM119, TREM2 and all other microglial associated genes. Thus, microglia-progenitor cells are found throughout the adult brain and can be stimulated to proliferate and differentiate into microglia using CSF1R inhibitors. We are now working to fully understand the properties and sources of these progenitors, and to assess their stem cell potentials.