Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions.
Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions.
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DOI：
10.1016/j.stem.2011.07.002
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发表时间：
2011-08-05
期刊：
影响因子：
23.9
通讯作者：
Ding S
中科院分区：
文献类型：
--
作者：
Ambasudhan R;Talantova M;Coleman R;Yuan X;Zhu S;Lipton SA;Ding S
人类诱导多能干细胞(HiPSCs)是通过使用各种方法对多种不同类型的体细胞重新编程而产生的。此外，将成熟细胞从一个谱系直接重新编程到另一个谱系是最近出现的一种产生感兴趣细胞类型的替代策略。在这里，我们证明了在精确定义的条件下，一个microRNA(miR-124)和两个转录因子(Myt1和Brn2)的组合足以直接将出生后和成人的原始真皮成纤维细胞(中胚层)重新编程为功能神经元(外胚层)。这些人类诱导神经元(HIN)表现出典型的神经元形态和标记基因表达、火动作电位，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换策略具有重要意义。
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.