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

Xing, YL; Poh, J; Chuang, BHA; Moradi, K; Mitew, S; Richardson, WD; Kilpatrick, TJ; ... Merson, TD; + view all (2023) High-efficiency pharmacogenetic ablation of oligodendrocyte progenitor cells in the adult mouse CNS. Cell Reports Methods , 3 (2) , Article 100414. 10.1016/j.crmeth.2023.100414. Green open access

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Abstract

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent CNS have limitations in the extent and duration of OPC depletion. We have developed a pharmacogenetic 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.

Type: Article
Title: High-efficiency pharmacogenetic ablation of oligodendrocyte progenitor cells in the adult mouse CNS
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.crmeth.2023.100414
Publisher version: https://doi.org/10.1016/j.crmeth.2023.100414
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Oligodendrocyte progenitor cells, neural precursor cells, cell ablation, regeneration, oligodendrocytes, NG2 glia, ventricular-subventricular zone, neural stem cells, diphtheria toxin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10166612
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