Trophoblast cells play an essential role in the interactions between the fetus and mother. Mouse trophoblast stem (TS) cells have been derived and used as the best in vitro model for molecular and functional analysis of mouse trophoblast lineages, but attempts to derive human TS cells have so far been unsuccessful. Here we show that activation of Wingless/Integrated (Wnt) and EGF and inhibition of TGF-β, histone deacetylase (HDAC), and Rho-associated protein kinase (ROCK) enable long-term culture of human villous cytotrophoblast (CT) cells. The resulting cell lines have the capacity to give rise to the three major trophoblast lineages, which show transcriptomes similar to those of the corresponding primary trophoblast cells. Importantly, equivalent cell lines can be derived from human blastocysts. Our data strongly suggest that the CT- and blastocyst-derived cell lines are human TS cells, which will provide a powerful tool to study human trophoblast development and function.

中文翻译：

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人滋养层干细胞的衍生。

滋养层细胞在胎儿与母亲之间的相互作用中起着至关重要的作用。小鼠滋养层干细胞（TS）已被获得，并被用作对小鼠滋养层谱系进行分子和功能分析的最佳体外模型，但是迄今为止，未能成功获得人TS细胞。在这里，我们显示了Wingless / Integrated（Wnt）和EGF的激活以及TGF-β，组蛋白脱乙酰基酶（HDAC）和Rho相关蛋白激酶（ROCK）的抑制使人绒毛滋养细胞（CT）细胞能够长期培养。所得的细胞系具有产生三种主要的滋养层细胞谱系的能力，它们显示出与相应的原代滋养层细胞相似的转录组。重要的是，等效细胞系可以源自人胚泡。