Abstract：
Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone (SVZ) throughout life, responding to various pathophysiological stimuli and playing a crucial role in central nervous system repair. Although numerous studies have elucidated the role of stanniocalcin 2 (STC2) in regulating cell differentiation processes, its specific function in NSPCs differentiation remains poorly understood. Clarifying the role of STC2 in NSPCs is essential for devising novel strategies to enhance the intrinsic potential for brain regeneration postinjury. Our study revealed the expression of STC2 in NSPCs derived from the SVZ of the C57BL/6N mouse. In cultured SVZ-derived NSPCs, STC2 treatment significantly increased the number of Tuj1 and DCX-positive cells. Furthermore, STC2 injection into the lateral ventricle promoted the neuronal differentiation of NSPCs and migration to the olfactory bulb. Conversely, the STC2 knockdown produced the opposite effect. Further investigation showed that STC2 treatment enhanced AKT phosphorylation in cultured NSPCs, whereas STC2 inhibition hindered AKT activation. Notably, the neuronal differentiation induced by STC2 was blocked by the AKT inhibitor GSK690693, whereas the AKT activator SC79 reversed the impact of STC2 knockdown on neuronal differentiation. Our findings indicate that enhancing STC2 expression in SVZ-derived NSPCs facilitates neuronal differentiation, with AKT regulation potentially serving as a key intracellular target of STC2 signaling.
摘要：
神经干/祖细胞（NSPCs）在哺乳动物的整个生命中持续存在，响应各种病理生理刺激，在中枢神经系统修复中起着至关重要的作用。尽管许多研究已经阐明了斯ninocalcin2（STC2）在调节细胞分化过程中的作用，其在NSPCs分化中的具体功能尚不清楚。明确STC2在NSPC中的作用对于设计新策略以增强损伤后脑再生的内在潜力至关重要。我们的研究揭示了STC2在C57BL/6N小鼠脑室下区（SVZ）的NSPCs中的表达。在培养的SVZ衍生的NSPC中，STC2处理显著增加了Tuj1和DCX阳性细胞的数量。此外，侧脑室注射STC2促进NSPCs的神经元分化和向嗅球的迁移。相反，STC2敲低产生相反的效果。进一步的研究表明，STC2处理增强了培养的NSPCs中的AKT磷酸化，而STC2抑制阻碍AKT激活。值得注意的是,STC2诱导的神经元分化被AKT抑制剂GSK690693阻断,而AKT激活剂SC79逆转STC2敲低对神经元分化的影响.我们的发现表明，增强SVZ衍生的NSPCs中的STC2表达促进神经元分化，AKT调节可能是STC2信号传导的关键细胞内靶标。
