Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell Stem Cell. 2011 Aug 5;9(2):113-8. doi: 10.1016/j.stem.2011.07.002. Epub 2011 Jul 28.
Human induced pluripotent stem cells (hiPSCs) have been generated by reprogramming a number of different somatic cell types using a variety of approaches. In addition, direct reprogramming of mature cells from one lineage to another has emerged recently as an alternative strategy for generating cell types of interest. Here we show that a combination of a microRNA (miR-124) and two transcription factors (MYT1L and BRN2) is sufficient to directly reprogram postnatal and adult human primary dermal fibroblasts (mesoderm) to functional neurons (ectoderm) under precisely defined conditions. These human induced neurons (hiNs) exhibit typical neuronal morphology and marker gene expression, fire action potentials, and produce functional synapses between each other. Our findings have major implications for cell-replacement strategies in neurodegenerative diseases, disease modeling, and neural developmental studies.
人类诱导多能干细胞（hiPSCs）已通过多种方法对多种不同的体细胞类型进行重编程生成。此外，最近出现了一种从一种谱系到另一种谱系的成熟细胞的直接重编程的替代策略，用于产生感兴趣的细胞类型。在这里，我们表明，miR-124 与两个转录因子（MYT1L 和 BRN2）的组合足以在精确定义的条件下直接将出生后和成年的人类原代真皮成纤维细胞（中胚层）重编程为功能性神经元（外胚层）。这些人诱导神经元（hiNs）表现出典型的神经元形态和标记基因表达，产生动作电位，并在彼此之间产生功能性突触。我们的发现对神经退行性疾病、疾病建模和神经发育研究中的细胞替代策略具有重大意义。
