Single cell atlas of amnion development of the first trimester of human pregnancy

The amnion is an essential extraembryonic tissue that maintains the intrauterine environment during pregnancy, yet its development remains enigmatic given the scarcity of samples from early-stage pregnancies. Here, we performed single-cell transcriptomic analysis of the amnion across three stages in the first trimester of pregnancy. We identified 13 distinct cell types, including amnion epithelial stem cells (AESCs), amnion mesenchymal stem cells (AMSCs), and several known and novel cell types. Epithelial lineages predominate in the early amnion, with mesenchymal and ectodermal, ectodermal cells arising later. We identify a population of bipotent progenitors that generates both AESCs and AMSCs. Trajectory and RNA velocity analyses of amniotic cells revealed epithelial, mesenchymal, and ectodermal trajectories. Moreover, the expression of secreted ligands uncovered four signaling patterns that change as development progresses. Finally, we detected mixed fetal and maternal blood and immune cells within the amnion. This cellular map highlights the landscape and complexity of the human amnion and serves as a resource for further studies of amnion development, physiology, and therapeutic applications.