Surviving microglia and nonmicroglial progenitors contribute to microglial repopulation following colony-stimulating factor 1 receptor inhibition.

Authors

Eric Yuhsiang Wang, Hank Szuhan Chen, Ya Lan Yang, Ching Mei Wu, Yi-Wen Chang, Ted Weita Lai

Published in

Neuroreport. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

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.
Using Cx3cr1CreER:Ai14 (tdTomato) reporter mice, we labeled microglia before PLX3397-induced depletion and assessed repopulation. Next, in Cx3cr1CreER+/-:Csf1rfl/fl mice, we combined tamoxifen-induced genetic CSF1R deletion with PLX3397 to ablate microglia completely and evaluated recovery.
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.
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.

PMID:
42322052
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.