High-efficiency pharmacogenetic ablation of oligodendrocyte progenitor cells in the adult mouse CNS

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the ro-dent CNS have limitations in the extent and duration of OPC depletion. We have developed a pharmacoge-netic approach for conditional OPC ablation, eliminating >98% of OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRA-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRA+NG2+ cells with the capacity to proliferate and migrate extensively throughout the dorsal anterior forebrain. Further application of this approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.

Automated summary

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) have limitations, but a pharmacogenetic approach for conditional OPC ablation eliminates the majority of OPCs throughout the brain. The depletion of OPCs induces V-SVZ-derived NPCs to generate a large number of proliferating and migrating PDGFRA+NG2+ cells. This approach will enhance our knowledge of the function of OPCs and oligodendrogenic NPCs in health and disease.