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NG2-expressing cells in the central nervous system consist of heterogeneous cell populations and proliferate rapidly in response to injuries,making them a promising cell source for the treatment of spinal cord injury.To elucidate their lineage potential and therapeutic value,we first generated NG2* cell clones and evaluated their differentiation capacity.In vitro differentiation analysis revealed that all the clones could differentiate into oligodendrocytes,and some of them were capable of differentiating into astrocytes as well.Interestingly,one clone exhibited a multipotent capacity for differentiating into not only neuronal and glial lineages,but also chondrocytes.These subtypes of NG2* cells also exhibit phenotypic heterogeneity according to a spectrum of neural progenitor markers (NG2,PDGFaR,Nestin,and A2B5).Collectively,these results suggest that NG2* cells contain heterogeneous progenitors with various differentiation capacities.We next explored the therapeutic role of neurogenesis using NG2* cells and epidermal growth factor receptor (EGFR) inhibition.In an experimental contusive spinal cord injury model,we found that the antagonizing function of EGFR with a specific EGFR inhibitor (PD168393) resulted in a significant amount of neuronal phenotypes from NG2+ cells (either in situ or through ex vivo transplantation) in mice with spinal cord injury,which presumably led to accumulation of newly-generated neurons.Additionally,by attenuating EGFR signaling in the injured niche,improved behavioral performance,histological recovery,reduced astrogliosis,and microglia and macrophages were also observed.Our results demonstrate that NG2* cells,well-known as glial progenitors,could be manipulated for repairing neuronat loss after spinal cord injury.These findings support the possibility of evoking endogenous neuronal replacement from NG2* cells and suggest that EGFR inhibition may be beneficial for treating central nervous system trauma.