Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
PLoS One. 2013 May 28;8(5):e64720. doi: 10.1371/journal.pone.0064720. Print 2013.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder mainly affecting motor neurons. Mutations in superoxide dismutase-1 (SOD-1) account for about 20% of familial ALS patients. A robust supply of motoneurons carrying the mutated gene would help understand the causes of motoneuron death and develop new therapeutics for the disease. Here, we established induced pluripotent stem (iPS) cell lines from SOD1G93A mice and compared their potency in motoneuron generation with normal iPS cells and mouse embryonic stem cells (E14). Our results showed that iPS cells derived from SOD1G93A mice possessed the similar potency in neuronal differentiation to normal iPS cells and E14 cells and can be efficiently driven to motoneuron-like phenotype. These cells exhibited typical neuronal morphology, expressed key motoneuron markers, including ChAT and HB9, and generated repetitive trains of action potentials. Furthermore, these neurons highly expressed human SOD-1 and exhibited shorter neurites compared to controls. The present study provides evidence that ALS-iPS cells can be used as disease models in high-throughput screening and mechanistic studies due to their ability to efficiently differentiate into specific neuronal subtypes.
肌萎缩侧索硬化症（ALS）是一种主要影响运动神经元的神经退行性疾病。超氧化物歧化酶-1（SOD-1）的突变约占家族性 ALS 患者的 20%。携带突变基因的运动神经元的大量供应将有助于了解运动神经元死亡的原因，并为该疾病开发新的治疗方法。在这里，我们从 SOD1G93A 小鼠中建立了诱导多能干细胞（iPS）细胞系，并将其与正常 iPS 细胞和小鼠胚胎干细胞（E14）在产生运动神经元的能力方面进行了比较。我们的结果表明，源自 SOD1G93A 小鼠的 iPS 细胞在神经元分化方面具有与正常 iPS 细胞和 E14 细胞相似的潜能，并且可以有效地被诱导为运动神经元样表型。这些细胞表现出典型的神经元形态，表达关键的运动神经元标志物，包括 ChAT 和 HB9，并产生重复的动作电位。此外，这些神经元高度表达人 SOD-1，与对照相比，其神经突较短。本研究提供的证据表明，由于 ALS-iPS 细胞能够高效分化为特定的神经元亚型，因此可以将其用作高通量筛选和机制研究的疾病模型。
