PDF(Pubmed)
Abstract：
A limited number of accessible and representative models of human trophoblast cells currently exist for the study of placentation. Current stem cell models involve either a transition through a naïve stem cell state or precise dynamic control of multiple growth factors and small-molecule cues. Here, we demonstrated that a simple five-day treatment of human induced pluripotent stem cells with two small molecules, retinoic acid (RA) and Wnt agonist CHIR 99021 (CHIR), resulted in rapid, synergistic upregulation of CDX2. Transcriptomic analysis of RA + CHIR-treated cells showed high similarity to primary trophectoderm cells. Multipotency was verified via further differentiation towards cells with syncytiotrophoblast or extravillous trophoblast features. RA + CHIR-treated cells were also assessed for the established criteria defining a trophoblast cell model, and they possess all the features necessary to be considered valid. Collectively, our data demonstrate a facile, scalable method for generating functional trophoblast-like cells in vitro to better understand the placenta.
摘要：
目前存在用于胎盘形成研究的有限数量的人类滋养层细胞的可访问和代表性模型。当前的干细胞模型涉及通过初始干细胞状态的过渡或对多种生长因子和小分子线索的精确动态控制。这里,我们证明了用两种小分子对人类诱导多能干细胞进行简单的五天治疗，维甲酸（RA）和Wnt激动剂CHIR99021（CHIR），导致快速，CDX2的协同上调。RACHIR处理的细胞的转录组学分析显示与原代滋养外胚层细胞高度相似。通过进一步分化为具有合胞体滋养层或绒毛外滋养层特征的细胞来验证多能性。还评估了RA+CHIR处理的细胞的确定标准，定义了滋养层细胞模型。它们具有被认为有效的所有必要特征。总的来说，我们的数据表明，在体外产生功能性滋养层样细胞的可扩展方法，以更好地了解胎盘。
