Stem Cells：转录因子Oct4可将滋养层干细胞重编程为多潜能干细胞
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《StemCells 干细胞》杂志在线发表文章,首次报道转录因子Oct4可以将滋养外胚层来源的滋养层干细胞重编程为具有分化为三胚层能力的多潜能干细胞.
滋养层干细胞（TS）和胚胎干细胞（ES）是从哺乳动物早期囊胚建立的两类干细胞,但是两种干细胞具有巨大的差异,首先滋养层干细胞来源于属于胚外组织的滋养外胚层细胞,而胚胎干细胞则来源于将来分化为原始内胚层和三胚层结构的内细胞团细胞.其次滋养层干细胞体内体外只能分化为胎盘细胞,而胚胎干细胞却可以分化为三胚层细胞.滋养层干细胞是否可以重编程（或转分化）为具有分化为三胚层能力的类胚胎干细胞还不清楚。
研究人员首先从不同品系小鼠建立了数株滋养层干细胞,并且经过体内体外分化实验鉴定了所建滋养层干细胞的分化潜能,即只能分化为胎盘细胞.进一步经过基因表达分析发现滋养层干细胞本身表达诸如Sox2,c-Myc基因,但是不表达Oct4,Klf4基因；进一步分析发现滋养层干细胞表达Esrrb基因,因为近期一篇研究论文证明Esrrb基因可以取代Klf4基因重编程成纤维细胞为iPS细胞,所以他们想是否可以利用少的因子甚至一个转录因子将滋养层干细胞转变为多潜能干细胞.他们利用Tet-on可诱导系统将不同的基因组合转入滋养层干细胞,最终证明一个转录因子Oct4就可以将滋养层干细胞重编程为类似于胚胎干细胞的多潜能干细胞,其间许多重要的表观遗传重编程事件诸如X染色体重新激活（X-chromosome reactivation）,多能性基因启动子区DNA去甲基化等都在细胞命运转变过程中发生,诱导形成的多潜能干细胞可以在体内外分化为三胚层结构的细胞类型,并且可以高效的产生具有生殖系传递能力的嵌合体小鼠。
滋养层干细胞是继神经干细胞之后第二类干细胞可以由一个转录因子Oct4（在不添加其它小分子抑制剂情况下）转变为多潜能干细胞,同时该研究也为进一步深入研究早期胚胎分化,细胞命运决定提供了重要的理论依据和研究思路.
推荐阅读原文：
Stem Cells. 2011 May;29(5):755-63. doi: 10.1002/stem.617.
Reprogramming of trophoblaststem cells into pluripotentstem cells by Oct4.
Abstract
ESCs and trophoblaststem (TS) cells are both derived from early embryos, yet these cells have distinct differentiation properties. ESCs candifferentiate into all three germ layer cell types, whereas TS cells can only differentiate into placental cells. It has not been determined whether TS cells can be converted into ES-like pluripotentstem (PS) cells. Here, we report thatoverexpression of a single transcription factor, Oct4, in TS cells is sufficient to reprogram TS cells into a pluripotent state.These Oct4-induced PS (OiPS) cells have the epigenetic characteristics of ESCs,including X chromosome reactivation, elevated H3K27 me3 modifications, andhypomethylation of promoter regions in Oct4 and Nanog genes. Meanwhile, methylation of promoterregion in the Elf5 gene occurred during reprogramming of TS cells. The gene expression profile of OiPS cells was very similar to ESCs. Moreover, OiPS cells can differentiate into the three germ layer celltypes in vitro and in vivo. More importantly, chimeric mice with germlinetransmission could be efficiently produced from OiPS cells. Our results demonstrate that one singletranscription factor, Oct4, could reprogram the nonembryonic TS cells into PS cells.