Department of Neurology, Northwestern University, Chicago, IL 60611, USA.
Department of Neurology, Northwestern University, Chicago, IL 60611, USA.
Cell Rep. 2021 May 18;35(7):109138. doi: 10.1016/j.celrep.2021.109138.
Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Here we report a protocol differentiating human pluripotent stem cells into endometrial stromal fibroblasts (PSC-ESFs) that are highly pure and able to decidualize. Coculture of PSC-ESFs with placenta-derived endometrial epithelial cells generated organoids used to examine stromal-epithelial interactions. Cocultures exhibited specific endometrial markers in the appropriate compartments, organization with cell polarity, and hormone responsiveness of both cell types. Furthermore, cocultures recapitulate a central feature of the human decidua by cyclically responding to hormone withdrawal followed by hormone retreatment. This advance enables mechanistic studies of the cyclic responses that characterize the human endometrium.
各种人类疾病和与妊娠相关的疾病都反映了子宫内膜功能障碍。然而，啮齿动物模型与人类子宫内膜没有共同的基本生物学过程，例如自发的蜕膜化，并且现有的人类细胞培养物不能重现蜕膜化和着床所必需的子宫内膜基质和上皮细胞之间的周期性相互作用。在这里，我们报告了一种将人类多能干细胞分化为子宫内膜基质成纤维细胞（PSC-ESF）的方案，这些细胞高度纯净且能够进行蜕膜化。将 PSC-ESF 与胎盘来源的子宫内膜上皮细胞共培养，生成用于研究基质-上皮相互作用的类器官。共培养物在适当的隔室中表现出特定的子宫内膜标记物、细胞极性的组织以及两种细胞类型的激素反应性。此外，共培养物通过周期性地对激素撤出后再用激素进行反应，重现了人类蜕膜的一个核心特征。这一进展使人们能够对周期性反应进行机制研究，这些反应是人类子宫内膜的特征。
