Sellers Drew L, Maris Don O, Horner Philip J
Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, USA.
J Neurosci. 2009 May 20;29(20):6722-33. doi: 10.1523/JNEUROSCI.4538-08.2009.
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.
表达NG2蛋白聚糖的祖细胞是中枢神经系统内主要的自我更新细胞。NG2祖细胞在完整的干细胞生态位内补充少突胶质细胞群体，而处于增殖周期的NG2细胞是最早对中枢神经系统损伤作出反应的细胞之一。我们研究了脊髓损伤后NG2祖细胞的作用，以及骨形态发生蛋白信号如何重塑损伤后（PI）的渐进性生态位。用NG2特异性报告病毒标记的子代细胞在分化谱上发生了协调变化。损伤后24小时产生的NG2子代细胞生成形成瘢痕的星形胶质细胞和新型吞噬性星形胶质细胞的短暂群体，这些吞噬性星形胶质细胞在组织蛋白酶D标记的内体中含有变性髓磷脂，但损伤后7天产生的NG2祖细胞分化为少突胶质细胞，并在包裹轴突的突起上表达髓磷脂。脊髓mRNA分析显示，影响PI重塑和直接祖细胞分化的配体的生态位转录组存在时间上的变化。我们得出结论，NG2子代细胞是不同的谱系，在创伤后遵循渐进性线索来补充受损的生态位。
