Zhuang Hong, Zhang Rong, Zhang Shujie, Shu Qinmeng, Zhang Dan, Xu Gezhi
Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.
Research Center, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.
Neurosci Lett. 2015 Jul 23;600:69-74. doi: 10.1016/j.neulet.2015.05.061. Epub 2015 Jun 3.
Mesenchymal stem cells (MSCs) have the capacity to generate multiple tissues of mesodermal origin, and also have the potential to trans-differentiate into neurons. We isolated MSCs from the Wharton's jelly of the human umbilical cord (WJ-MSCs), and efficiently induced WJ-MSCs into neuron-like cells using a modified method. After neuronal induction for 12 days, most of WJ-MSCs expressed mature neuronal marker MAP2 (83 ± 7%), and meanwhile some adopted neuronal morphology. WJ-MSCs also expressed Nestin (34 ± 6%), NSE (30 ± 5%), and GFAP (12 ± 3%). Moreover, we used miRNA microarray to analyze the differentially expressed miRNAs in neuronal differentiation of WJ-MSCs. Microarray analysis revealed discrepant miRNA profiles in the uninduced WJ-MSCs and WJ-MSCs derived neurons. Six miRNAs were chosen for further qRT-PCR validation. Among these 6 miRNAs, four miRNAs (miR-1290, miR-26b, miR-194, and miR-124a) were up-regulated and 2 miRNAs (miR-4521 and miR-543) were down-regulated in the WJ-MSCs derived neurons. In conclusion, WJ-MSCs could be efficiently induced into neuron-like cells. More importantly, our findings suggested that miRNAs might play important roles in the neuronal differentiation of WJ-MSCs.
间充质干细胞(MSCs)具有生成多种中胚层来源组织的能力,并且也有转分化为神经元的潜力。我们从人脐带华通氏胶中分离出MSCs(WJ-MSCs),并使用改良方法将WJ-MSCs高效诱导为神经元样细胞。神经元诱导12天后,大多数WJ-MSCs表达成熟神经元标志物MAP2(83±7%),同时一些呈现神经元形态。WJ-MSCs还表达巢蛋白(Nestin,34±6%)、神经元特异性烯醇化酶(NSE,30±5%)和胶质纤维酸性蛋白(GFAP,12±3%)。此外,我们使用miRNA微阵列分析WJ-MSCs神经元分化过程中差异表达的miRNA。微阵列分析揭示了未诱导的WJ-MSCs和源自WJ-MSCs的神经元中不同的miRNA谱。选择6种miRNA进行进一步的qRT-PCR验证。在这6种miRNA中,4种miRNA(miR-1290、miR-26b、miR-194和miR-124a)在源自WJ-MSCs的神经元中上调,2种miRNA(miR-4521和miR-543)下调。总之,WJ-MSCs可以被高效诱导为神经元样细胞。更重要的是,我们的研究结果表明miRNA可能在WJ-MSCs的神经元分化中发挥重要作用。