Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Cell Stem Cell. 2012 Jul 6;11(1):100-9. doi: 10.1016/j.stem.2012.05.018. Epub 2012 Jun 7.
The generation of induced pluripotent stem cells (iPSCs) and induced neuronal cells (iNCs) from somatic cells provides new avenues for basic research and potential transplantation therapies for neurological diseases. However, clinical applications must consider the risk of tumor formation by iPSCs and the inability of iNCs to self-renew in culture. Here we report the generation of induced neural stem cells (iNSCs) from mouse and human fibroblasts by direct reprogramming with a single factor, Sox2. iNSCs express NSC markers and resemble wild-type NSCs in their morphology, self-renewal, ability to form neurospheres, and gene expression profiles. Cloned iNSCs differentiate into several types of mature neurons, as well as astrocytes and oligodendrocytes, indicating multipotency. Implanted iNSCs can survive and integrate in mouse brains and, unlike iPSC-derived NSCs, do not generate tumors. Thus, self-renewable and multipotent iNSCs without tumorigenic potential can be generated directly from fibroblasts by reprogramming.
诱导多能干细胞（iPSCs）和诱导神经元细胞（iNCs）的体细胞生成，为神经疾病的基础研究和潜在的移植治疗提供了新途径。然而，临床应用必须考虑 iPSCs 形成肿瘤的风险，以及 iNCs 在培养中自我更新的能力。在这里，我们报告了通过单一因子 Sox2 直接重编程，从小鼠和人成纤维细胞中生成诱导神经干细胞（iNSCs）。iNSCs 表达 NSC 标记物，其形态、自我更新能力、形成神经球的能力和基因表达谱与野生型 NSCs 相似。克隆的 iNSCs 分化为多种成熟神经元以及星形胶质细胞和少突胶质细胞，表明其具有多能性。植入的 iNSCs 可以在小鼠大脑中存活并整合，与 iPSC 衍生的 NSCs 不同，它们不会产生肿瘤。因此，具有自我更新和多能性且无致瘤性的 iNSCs 可以通过重编程直接从成纤维细胞中产生。
