Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury.
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.
Sellers
Drew L
DL
Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, USA. drewfus@u.washington.edu
Maris
Don O
DO
Horner
Philip J
PJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D055153:Stem Cell Niche / Q000473:pathology* / Q000503:physiopathology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D053148:Caspase 3; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D011509:Proteoglycans; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4