Yang Yuanyuan, Jiao Jiao, Gao Rui, Yao Hui, Sun Xiao-Fang, Gao Shaorong
1 Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical College , Guangdong, 510150, P.R. China .
Cell Reprogram. 2013 Dec;15(6):484-9. doi: 10.1089/cell.2013.0013. Epub 2013 Nov 4.
Ectopic expression of a set of transcription factors in somatic cells could reprogram the differentiated cell fate into the pluripotent state, and the resultant so-called induced pluripotent stem cells (iPSCs) have been proposed as seed cells for cell therapy-based regenerative medicine. However, their tumorigenicity limited the further application of iPSCs clinically. More recently, collected evidence has shown that differentiated somatic cells could be directly converted into other types of somatic cells through overexpression of transcription factors enriched in the targeted cell types. Induced neurons have been recently converted from fibroblasts; however, it remains unknown if other cell types could be used for neuron induction. One easily accessible cell type, adipocyte progenitor cells (APCs), has the advantage of steady proliferation in vitro and lower mortality rate. In the present study, we demonstrated that APCs could also be converted into functional neurons using the three transcriptional factors (Ascl1, Brn2, Myt1l) that could convert fibroblasts into neurons. Moreover, we also demonstrated that vitamin C could elevate the efficiency of conversion of the APCs and fibroblasts into neurons. The converted cells represent another appropriate cell resource for clinical application and disease modeling.
在体细胞中异位表达一组转录因子可将分化的细胞命运重编程为多能状态,由此产生的所谓诱导多能干细胞(iPSCs)已被提议作为基于细胞治疗的再生医学的种子细胞。然而,它们的致瘤性限制了iPSCs在临床上的进一步应用。最近,越来越多的证据表明,通过过表达在目标细胞类型中富集的转录因子,分化的体细胞可以直接转化为其他类型的体细胞。最近已从成纤维细胞诱导生成了神经元;然而,其他细胞类型是否可用于神经元诱导仍不清楚。一种易于获取的细胞类型,脂肪细胞祖细胞(APCs),具有在体外稳定增殖和较低死亡率的优势。在本研究中,我们证明,使用可将成纤维细胞转化为神经元的三种转录因子(Ascl1、Brn2、Myt1l),APCs也可以转化为功能性神经元。此外,我们还证明,维生素C可以提高APCs和成纤维细胞向神经元的转化效率。转化后的细胞是临床应用和疾病建模的另一种合适的细胞资源。