人类胎盘──胎儿产生的胎外膜器官，与宫腔黏膜层──子宫内的黏膜层，之间的关系在妊娠期间的胎儿滋养和保护中是至关重要的。源自胎盘绒毛的绒毛外胚层细胞（EVTs）浸润到宫腔黏膜层中，将母体动脉转化为高传导血管1。胎盘绒毛侵入和动脉转化的缺陷，是早期妊娠期间常见妊娠疾病，如先兆子痫2的根源。本文生成了整个人类母体-胎儿界面的空间多组学单细胞图谱，包括子宫肌层，使我们能够解析绒毛外胚层细胞分化的完整轨迹。我们利用这个细胞地图来推断可能调节EVT浸润的转录因子，并表明它们在EVT原代器官oid3、4和EVT干细胞5的体外分化模型中得到保留。我们定义了绒毛侵入的最终细胞状态的转录组：胎盘床巨细胞（融合的多核EVTs）和内血管EVTs（在母体动脉内形成堵塞物）。我们预测了绒毛侵入和胎盘床巨细胞形成所涉及的细胞间通讯事件，并对EVTs对早期妊娠期间动脉转化的间质型EVTs和内血管型EVTs的双重作用进行了建模。总之，我们的数据提供了一个关于植入后绒毛外胚层细胞分化的全面分析，可以用于指导早期妊娠期间的人类胎盘的实验模型设计。© 2023年，作者（们）

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal-fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell-cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.© 2023. The Author(s).