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NG2+ oligodendrocyte progenitor cells (OPCs) are a unique cell population that proliferates in response to central nervous system (CNS) injuries. OPCs can not only differentiate into myelinating oligodendrocytes after spinal cord injury (SCI) but also proliferate near the lesion and therefore may play a role in glial scar formation. We utilized a novel transgenic mouse model that selectively deletes OPCs to determine the effects of OPC loss on glial and fibrotic scar formation after SCI. This model crosses pdgfrDTR mice to Olig2-cre mice to generate a transgenic mouse line (Olig2-DTR) expressing human diphtheria toxin receptor (hDTR) only in Olig2+PDGFRa+ cells (OPCs). To delete OPCs in Olig2-DTR mice, we injected 20ng/g of diphtheria toxin (DT) daily (0.4g in 100 sterile saline for a 20g mouse). Olig2-WT littermates received the same regimen; since these mice do not express hDTR, they should be unaffected by the drug. In naïve Olig2-DTR mice treated with DT, NG2+ cells were reduced by over 50% in the cervical spinal cord (n = 12) compared to Olig2-WT mice (n = 9). Next, the effects of OPC deletion on glial scar formation and stabilization after SCI were examined. Mice received a C5 unilateral contusion with a 60 kD force and were treated with DT daily, and tissue was assessed at 7, 11, or 21 days post-injury (dpi) – key times for glial scar formation. At 7dpi, OPCs were significantly depleted around the lesion border in Olig2-DTR mice (n=5) compared to Olig2-WT littermate controls (n=4). Olig2-DTR mice had significantly larger lesion sizes compared to controls, and GFAP expression within the lesion border was three times lower in Olig2-DTR mice. Additionally, GFAP width around the border was significantly decreased in Olig2-DTR versus Olig2-WT mice. Depletion of OPCs also significantly reduced laminin expression within the lesion core at 7d post-injury. At 11dpi, GFAP expression within the lesion border was significantly decreased in Olig2-DTR mice (n=6) versus Olig2-WT littermates (n=6). However, there were no significant differences in lesion size, glial scar width, and laminin expression between the two groups. The 21dpi cohorts received daily DT injections for 14dpi followed by 7d of no treatment. DT injections for 14 days cover the time of peak OPC proliferation. Analysis of this cohort is ongoing and will clarify how early OPC deletion alters longer-term glial scar formation and composition. Together, these results indicate a novel role for OPCs in contributing to glial scar formation and lesion stabilization after traumatic SCI.