Zhu Jianguo, Pang Daxin, Zhou Yang, Tang Xiaochun, Huang Yongye, Xie Wanhua, Gao Fei, Lai Liangxue, Zhang Mingjun, Ouyang Hongsheng
Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
Cell Reprogram. 2012 Apr;14(2):99-105. doi: 10.1089/cell.2011.0074. Epub 2012 Feb 28.
Direct reprogramming of terminally differentiated cells to specify different cell types may allow somatic cells to be reprogrammed to an alternative, differentiated fate without intervening stem or progenitor cells. Recent studies have shown that the conversion of fibroblasts to other cell lines can be accomplished by the introduction of master regulator transcription factors. These findings have raised the question as to whether chemical molecules could replace transcription factor cocktails to directly alter defined somatic cell fate. Here, we demonstrate the generation of adipocytes directly from porcine embryonic fibroblasts (PEFs) using defined chemical molecules. Treatment with SB431542 and Thiazovivin, which are transforming growth factor-beta (TGF-β) and ROCK signaling pathway inhibitors, respectively, allowed PEFs to directly convert to fat-laden adipocytes. These induced adipocytes expressed multiple fat marker genes. We believe that these findings demonstrate that committed adipocytes can be directly reprogrammed from differentiated somatic cells using defined chemical molecules. The generation of adipocytes from nonadipogenic lineages has important implications for studies of adipogenesis, obesity modeling, and regenerative medicine. Additionally, these findings may enlighten a new method that direct reprogramming committed cell lines to other somatic cells using defined chemical molecules.
将终末分化细胞直接重编程以指定不同细胞类型，可能使体细胞在不经过中间干细胞或祖细胞的情况下重编程为另一种分化命运。最近的研究表明，通过引入主控调节转录因子，可以将成纤维细胞转化为其他细胞系。这些发现引发了一个问题，即化学分子是否可以替代转录因子组合来直接改变特定的体细胞命运。在此，我们证明了使用特定化学分子可直接从猪胚胎成纤维细胞（PEF）生成脂肪细胞。分别用转化生长因子-β（TGF-β）和ROCK信号通路抑制剂SB431542和噻唑烷二酮处理，可使PEF直接转化为充满脂肪的脂肪细胞。这些诱导产生的脂肪细胞表达多种脂肪标记基因。我们认为，这些发现表明，使用特定化学分子可将已分化的体细胞直接重编程为脂肪细胞。从非脂肪生成谱系生成脂肪细胞对脂肪生成、肥胖建模和再生医学研究具有重要意义。此外，这些发现可能启发一种新方法，即使用特定化学分子将已分化的细胞系直接重编程为其他体细胞。
