Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nat Cell Biol. 2012 Sep;14(9):892-9. doi: 10.1038/ncb2567.
Lineage conversion has recently attracted increasing attention as a potential alternative to the directed differentiation of pluripotent cells to obtain cells of a given lineage. Different means allowing for cell identity switch have been reported. Lineage conversion relied initially on the discovery of specific transcription factors generally enriched and characteristic of the target cell, and their forced expression in cells of a different fate. This approach has been successful in various cases, from cells of the hematopoietic systems to neurons and cardiomyocytes. Furthermore, recent reports have suggested the possibility of establishing a general lineage conversion approach bypassing pluripotency. This requires a first phase of epigenetic erasure achieved by short overexpression of the factors used to reprogram cells to a pluripotent state (such as a combination of Sox2, Klf4, c-Myc and Oct4), followed by exposure to specific developmental cues. Here we present these different direct conversion methodologies and discuss their potential as alternatives to using induced pluripotent stem cells and differentiation protocols to generate cell populations of a given fate.
谱系转换最近作为一种替代定向分化多能细胞以获得特定谱系细胞的方法引起了越来越多的关注。已经报道了不同的允许细胞身份转换的方法。谱系转换最初依赖于发现通常在靶细胞中富集和特征性表达的特定转录因子，并在不同命运的细胞中强制表达这些转录因子。这种方法在各种情况下都取得了成功，从造血系统的细胞到神经元和心肌细胞。此外，最近的报告表明，有可能建立一种绕过多能性的通用谱系转换方法。这需要通过短时间过表达用于将细胞重编程为多能状态的因子（如 Sox2、Klf4、c-Myc 和 Oct4 的组合）来实现初始的表观遗传擦除阶段，然后再暴露于特定的发育线索。在这里，我们介绍了这些不同的直接转换方法，并讨论了它们作为替代使用诱导多能干细胞和分化方案来产生特定命运的细胞群体的潜力。
