Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Sci Rep. 2019 Nov 13;9(1):16707. doi: 10.1038/s41598-019-53007-6.
Transdifferentiation of other cell type into human neuronal cells (hNCs) provides a platform for neural disease modeling, drug screening and potential cell-based therapies. Among all of the cell donor sources, human urine cells (hUCs) are convenient to obtain without invasive harvest procedure. Here, we report a novel approach for the transdifferentiation of hUCs into hNCs. Our study demonstrated that a combination of seven small molecules (CAYTFVB) cocktail induced transdifferentiation of hUCs into hNCs. These chemical-induced neuronal cells (CiNCs) exhibited typical neuron-like morphology and expressed mature neuronal markers. The neuronal-like morphology revealed in day 1, and the Tuj1-positive CiNCs reached to about 58% in day 5 and 38.36% Tuj1+/MAP2+ double positive cells in day 12. Partial electrophysiological properties of CiNCs was obtained using patch clamp. Most of the CiNCs generated using our protocol were glutamatergic neuron populations, whereas motor neurons, GABAergic or dopaminergic neurons were merely detected. hUCs derived from different donors were converted into CiNCs in this work. This method may provide a feasible and noninvasive approach for reprogramming hNCs from hUCs for disease models and drug screening.
将其他类型的细胞转化为人类神经元细胞(hNCs)为神经疾病建模、药物筛选和潜在的基于细胞的治疗提供了一个平台。在所有的细胞供体来源中,人类尿液细胞(hUCs)是方便获得的,不需要进行有创性的采集程序。在这里,我们报告了一种将 hUC 转化为 hNC 的新方法。我们的研究表明,七种小分子(CAYTFVB)鸡尾酒的组合诱导 hUC 转化为 hNC。这些化学诱导的神经元细胞(CiNCs)表现出典型的神经元样形态,并表达成熟的神经元标志物。CiNCs 在第 1 天表现出神经元样形态,Tuj1 阳性的 CiNCs 在第 5 天达到约 58%,第 12 天达到约 38.36%的 Tuj1+/MAP2+双阳性细胞。使用膜片钳技术获得了 CiNCs 的部分电生理特性。使用我们的方案产生的 CiNCs 大多数是谷氨酸能神经元群体,而运动神经元、GABA 能神经元或多巴胺能神经元仅被检测到。本工作中来自不同供体的 hUC 被转化为 CiNCs。这种方法可能为从 hUC 中重编程 hNC 以用于疾病模型和药物筛选提供一种可行的、非侵入性的方法。