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The Journal of Neuroscience, May 20, 2009, 29(20):6722-6733; doi:10.1523/JNEUROSCI.4538-08.2009

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Development/Plasticity/Repair
Postinjury Niches Induce Temporal Shifts in Progenitor Fates to Direct Lesion Repair after Spinal Cord Injury

Drew L. Sellers,¹ Don O. Maris,¹ and Philip J. Horner^1,2

¹Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, and ²Neurobiology and Behavior Program, University of Washington, Seattle, Washington 98015

Correspondence should be addressed to either Drew L. Sellers or Philip J. Horner, Department of Neurological Surgery, 325 9th Avenue, Box 359655, Seattle, WA 98104, Email: drewfus{at}u.washington.edu or Email: phorner{at}u.washington.edu

Progenitors that express NG2-proteoglycan are the predominant self-renewing cells within the CNS. NG2 progenitors replenish oligodendrocyte populations within the intact stem cell niche, and cycling NG2 cells are among the first cells to react to CNS insults. We investigated the role of NG2 progenitors after spinal cord injury and how bone morphogen protein signals remodel the progressive postinjury (PI) niche. Progeny labeled by an NG2-specific reporter virus undergo a coordinated shift in differentiation profile. NG2 progeny born 24 h PI produce scar-forming astrocytes and transient populations of novel phagocytic astrocytes shown to contain denatured myelin within cathepsin-D-labeled endosomes, but NG2 progenitors born 7 d PI differentiate into oligodendrocytes and express myelin on processes that wrap axons. Analysis of spinal cord mRNA shows a temporal shift in the niche transcriptome of ligands that affect PI remodeling and direct progenitor differentiation. We conclude that NG2 progeny are diverse lineages that obey progressive cues after trauma to replenish the injured niche.

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Received Sept. 22, 2008; revised Feb. 20, 2009; accepted April 13, 2009.

Correspondence should be addressed to either Drew L. Sellers or Philip J. Horner, Department of Neurological Surgery, 325 9th Avenue, Box 359655, Seattle, WA 98104, Email: drewfus{at}u.washington.edu or Email: phorner{at}u.washington.edu

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