Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain.
Stem Cells. 2012 Aug;30(8):1696-702. doi: 10.1002/stem.1138.
The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network.
使用定义因子对体细胞进行重编程以获得多能性的效率受到起始细胞类型的显著影响。在这里，我们表明，与其他常用于重编程的体细胞相比，人类角质形成细胞（其可被更高效率地重编程[Nat Biotechnol 2008;26:1276-1284]）与人类胚胎干细胞（ESC）共享更多在 CpG 上超甲基化的基因。此外，与由成纤维细胞（FiPS）重编程的多能细胞相比，由角质形成细胞（KiPS）重编程的多能细胞在 DNA 甲基化水平上与 ESC 更相似，这主要是由于存在那些在 FiPS 细胞中未能获得高 DNA 甲基化水平的基因。我们提出，更高的重编程效率与组织特异性基因的超甲基化相关，而不是与更易许可的多能性基因网络相关。
