Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.
Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY 12144.
Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2115709119. doi: 10.1073/pnas.2115709119. Epub 2022 May 10.
The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system have hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only morphology and global gene expression profiles comparable to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into functional extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from preexisting primed PSCs and provide a valuable opportunity to study human placenta development and pathology from patients with placenta-related diseases.
胎盘是一种短暂但重要的多功能器官，对母亲和胎儿的健康妊娠至关重要。然而，由于获取人类胎盘样本的途径有限，以及缺乏适当的体外模型系统，我们对早期人类胎盘发育和与胎盘相关的妊娠并发症的机制的理解受到了阻碍。为了克服这些限制，我们在滋养层干细胞培养基（TSCM）中建立了一种简单的短期骨形态发生蛋白 4（BMP4）处理程序，将人类初始多能干细胞（PSCs）转化为滋养层干细胞样细胞（TSLCs）。这些 TSLCs 不仅具有与真正的人类滋养层干细胞（TSCs）相当的形态和全局基因表达谱，而且具有长期自我更新能力和双能性，使细胞能够分化为功能性的绒毛外滋养细胞（EVT）和合体滋养细胞（ST）。这些表明 TSLCs 等同于真正的人类 TSCs。我们的数据表明，有一种直接的方法可以从现有的初始 PSCs 中生成人类 TSCs，为从患有胎盘相关疾病的患者中研究人类胎盘发育和病理学提供了宝贵的机会。
