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Updated: Jun 21, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Surviving microglia and nonmicroglial progenitors contribute to microglial repopulation following colony-stimulating
Eric Yuhsiang Wang1,2,3, Hank Szuhan Chen2, Ya Lan Yang1
1Graduate Institute of Biomedical Sciences.
Background:
Microglial repopulation after depletion via colony-stimulating factor 1 receptor (CSF1R) inhibition holds therapeutic potential for neurological disorders, but the cellular sources remain debated. We investigated whether repopulation arises solely from surviving microglia or also from nonmicroglial progenitors.
Methods:
Using Cx3cr1 CreER :Ai14 (tdTomato) reporter mice, we labeled microglia before PLX3397-induced depletion and assessed repopulation. Next, in Cx3cr1 CreER+/- :Csf1r fl/fl mice, we combined tamoxifen-induced genetic CSF1R deletion with PLX3397 to ablate microglia completely and evaluated recovery.
Results:
We found that repopulated microglia were predominantly tdTomato + , indicating derivation from surviving Cx3cr1 + microglia. Combined tamoxifen and PLX3397 achieved near-complete ablation, yet microglia repopulated and were re-depletable by PLX3397, confirming potential nonmicroglial origins.
Conclusion:
Microglial repopulation primarily involves proliferation of surviving microglia but can recruit nonmicroglial progenitors when depletion is exhaustive. These insights resolve prior inconsistencies and guide therapeutic strategies for microglial replacement treatment.
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