Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, CNM, Instituto de Salud Carlos III, Majadahonda, Spain.
Stem Cells. 2012 Dec;30(12):2796-809. doi: 10.1002/stem.1243.
Adult neural stem cells (NSCs) located in the subventricular zone (SVZ) persistently produce new neurons destined to the olfactory bulb (OB). Recent research suggests that the OB is also a source of NSCs that remains largely unexplored. Using single/dual-labeling procedures, we address the existence of NSCs in the innermost layers of the OB. In vivo, these cells are more quiescent that their SVZ counterparts, but after in vitro expansion, they behave similarly. Self-renewal and proliferation assays in co-culture with niche astrocytes indicate that OB-glia restricts NSC activity whereas SVZ-glia has the opposite effect. Gene expression profiling identifies WNT7A as a key SVZ-glial factor lacking in OB-glia that enhances self-renewal, thereby improving the propagation of OB-NSC cultures. These data demonstrate that region-specific glial factors account for in vivo differences in NSC activity and point to WNT7A as a tool that may be instrumental for the NSC expansion phase that precedes grafting.
成年神经干细胞（NSCs）位于侧脑室下区（SVZ），持续产生新的神经元，这些神经元定向迁移到嗅球（OB）。最近的研究表明，OB 也是 NSCs 的来源之一，但其仍未得到充分探索。通过单/双标记程序，我们研究了 OB 最内层是否存在 NSCs。在体内，这些细胞比其 SVZ 对应物更静止，但在体外扩增后，它们的行为相似。与龛状星形胶质细胞共培养的自我更新和增殖实验表明，OB-胶质细胞限制 NSC 活性，而 SVZ-胶质细胞则有相反的效果。基因表达谱分析表明 WNT7A 是 SVZ-胶质细胞的关键因子，而 OB-胶质细胞中缺乏 WNT7A 因子，该因子可增强自我更新，从而提高 OB-NSC 培养物的增殖。这些数据表明，特定区域的胶质细胞因子解释了 NSC 活性的体内差异，并指出 WNT7A 可能是移植前 NSC 扩增阶段的重要工具。
