@article{2039467fa556421b9c1f4913c90eba63,
title = "High-efficiency pharmacogenetic ablation of oligodendrocyte progenitor cells in the adult mouse CNS",
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.",
keywords = "cell ablation, CP: neuroscience, diphtheria toxin, neural precursor cells, neural stem cells, NG2 glia, oligodendrocyte progenitor cells, oligodendrocytes, regeneration, ventricular-subventricular zone",
author = "Xing, {Yao Lulu} and Jasmine Poh and Chuang, {Bernard H.A.} and Kaveh Moradi and Stanislaw Mitew and Richardson, {William D.} and Kilpatrick, {Trevor J.} and Yasuyuki Osanai and Merson, {Tobias D.}",
note = "Funding Information: This work was supported by the Australian Research Council Special Research Initiative – Stem Cells Australia (T.D.M., T.J.K.) and was supported in part by the Intramural Research Program of the National Institute of Mental Health ( NIMH ). Y.L.X. received support from the Cass Foundation ( 8545 ). T.D.M. was the recipient of a Future Fellowship from the Australian Research Council ( FT150100207 ) and received philanthropic support from Metal Manufactures Ltd. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. We thank Prof. Ryoichiro Kageyama (RIKEN Center for Brain Science, Japan) for generously providing the Nestin-CreER T2 (line 5.1) mice. We thank Prof. Nicoletta Kessaris (University College London, UK) for generously providing the Sox10-lox-GFP-poly(A)-lox-DTA mice. We thank Sun Jung Kang (NIMH, National Institutes of Health [NIH]) for advice on probability calculations. We acknowledge the use of facilities within the Monash Animal Research Platform, Monash Micro Imaging Platform, Monash Histology Platform, and Micromon (Monash University). Funding Information: This work was supported by the Australian Research Council Special Research Initiative – Stem Cells Australia (T.D.M. T.J.K.) and was supported in part by the Intramural Research Program of the National Institute of Mental Health (NIMH). Y.L.X. received support from the Cass Foundation (8545). T.D.M. was the recipient of a Future Fellowship from the Australian Research Council (FT150100207) and received philanthropic support from Metal Manufactures Ltd. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. We thank Prof. Ryoichiro Kageyama (RIKEN Center for Brain Science, Japan) for generously providing the Nestin-CreERT2 (line 5.1) mice. We thank Prof. Nicoletta Kessaris (University College London, UK) for generously providing the Sox10-lox-GFP-poly(A)-lox-DTA mice. We thank Sun Jung Kang (NIMH, National Institutes of Health [NIH]) for advice on probability calculations. We acknowledge the use of facilities within the Monash Animal Research Platform, Monash Micro Imaging Platform, Monash Histology Platform, and Micromon (Monash University). Conceptualization, Y.L.X. and T.D.M.; methodology, Y.L.X. and T.D.M.; investigation, Y.L.X. Y.O. J.P. B.H.A.C. K.M. S.M. and T.D.M; resources, W.D.R.; writing – original draft, Y.L.X. and T.D.M.; writing – review & editing, Y.L.X. W.D.R. T.J.K. and T.D.M.; supervision, T.D.M.; funding acquisition, T.D.M. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023",
year = "2023",
month = feb,
day = "27",
doi = "10.1016/j.crmeth.2023.100414",
language = "English",
volume = "3",
journal = "Cell Reports Methods",
issn = "2667-2375",
publisher = "Cell Press",
number = "2",
}