Zhu Ling-Ling, Zhao Tong, huang Xin, Liu Zhao-hui, Wu Li-ying, Wu Kui-wu, Fan Ming
Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, No. 27 Taiping Road, Beijing, People's Republic of China.
Cell Reprogram. 2011 Apr;13(2):113-20. doi: 10.1089/cell.2010.0043.
Hypoxia promotes the proliferation of neural progenitor cells (NPCs), and low oxygen is a useful tool for expansion of NPCs in vitro. To further understand the regulation of the mechanisms involved, we first identified the gene expression profile of NPCs and characterized their metabolic changes in vitro under 3% oxygen. NPCs derived from E13.5 rat mesencephalon were cultured under either normoxia or hypoxia for 24 h and 72 h. Total RNA was subjected to cDNA microarray analysis of 5705 genes. The results showed that approximately 1.24% of gene expression changed under low oxygen at the two time points. Among the 142 differentially expressed genes, the greatest number was involved in glycolysis and metabolism. The metabolic changes of NPCs under low oxygen conditions were also assayed. The glucose content in the conditioned medium incubated in low oxygen decreased significantly; however, the levels of pyruvate and lactic acid increased compared to conditioned medium cultured in normoxia. The NPCs under low oxygen consumed more glucose and produced energy by glycolysis. The information gained from gene expression and metabolic analyses of NPCs under low oxygen conditions will provide new approaches for the evaluation of NPCs as potential in vivo cellular therapeutics.
缺氧促进神经祖细胞(NPCs)的增殖,低氧是体外扩增NPCs的一种有用工具。为了进一步了解其中涉及的机制调控,我们首先鉴定了NPCs的基因表达谱,并表征了它们在3%氧气条件下体外的代谢变化。将源自E13.5大鼠中脑的NPCs在常氧或缺氧条件下培养24小时和72小时。对5705个基因的总RNA进行cDNA微阵列分析。结果表明,在这两个时间点,低氧条件下约1.24%的基因表达发生了变化。在142个差异表达基因中,数量最多的涉及糖酵解和代谢。还检测了低氧条件下NPCs的代谢变化。低氧条件下孵育的条件培养基中的葡萄糖含量显著降低;然而,与常氧培养的条件培养基相比,丙酮酸和乳酸水平升高。低氧条件下的NPCs消耗更多葡萄糖并通过糖酵解产生能量。从低氧条件下NPCs的基因表达和代谢分析中获得的信息将为评估NPCs作为潜在的体内细胞治疗方法提供新的途径。