Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Sci Rep. 2024 Aug 6;14(1):18204. doi: 10.1038/s41598-024-68952-0.
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.
目前，用于研究胎盘形成的可及性和代表性的人类滋养层细胞模型数量有限。目前的干细胞模型要么涉及到原始干细胞状态的转变，要么涉及到多种生长因子和小分子线索的精确动态控制。在这里，我们证明了用两种小分子视黄酸（RA）和 Wnt 激动剂 CHIR 99021（CHIR）对人诱导多能干细胞进行为期五天的简单处理，可快速协同上调 CDX2。RA+CHIR 处理细胞的转录组分析显示与原代滋养层细胞高度相似。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。还对 RA+CHIR 处理的细胞进行了评估，以确定定义滋养层细胞模型的既定标准，它们具有被认为是有效的所有特征。总的来说，我们的数据证明了一种简便、可扩展的方法，可在体外生成功能性类滋养层细胞，以更好地理解胎盘。
