From the Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Beijing 100049, China.
the Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
J Biol Chem. 2017 Nov 17;292(46):19122-19132. doi: 10.1074/jbc.M117.812537. Epub 2017 Sep 21.
We report here an approach to redirecting somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts to epithelial-like cells with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting epithelial-like cells that can be further reprogrammed to endodermal progenitor cells. Interestingly, these cells can self-renew and further differentiate into albumin-producing hepatocytes that can rescue mice from acute liver injury. Our results demonstrate a rational approach to convert mouse embryonic fibroblasts to hepatocytes and suggest that this mechanism-driven approach may be generalized for other cells.
我们在此报告了一种在化学定义条件下无需转录因子即可重定向体细胞命运的方法。我们首先用化学物质和生长因子将小鼠胚胎成纤维细胞转化为上皮样细胞。随后的细胞命运图谱显示，在得到的上皮样细胞中，SOX17 被强烈诱导，并且可以进一步被重编程为内胚层祖细胞。有趣的是，这些细胞可以自我更新，并进一步分化为产生白蛋白的肝细胞，可以使急性肝损伤的小鼠得到拯救。我们的结果证明了一种将小鼠胚胎成纤维细胞转化为肝细胞的合理方法，并表明这种基于机制的方法可能适用于其他细胞。
