Hu Wenqi, Sancho-Serra Carmen, Gantner Carlos W, Szafranska Hanna M, Solanky Nita, Metcalfe Kate, Vento-Tormo Roser, Zernicka-Goetz Magdalena
Plasticity and Self-Organization Group, Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Nat Cell Biol. 2025 Jul 14. doi: 10.1038/s41556-025-01696-9.
The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial-mesenchymal and epithelial-immune transitions, highlighting dynamic remodelling during early pregnancy. Our results further revealed key intercellular communication pathways, including BMP4 signalling from mesenchymal to epithelial cells and TGF-β signalling from macrophages to mesenchymal cells, suggesting coordinated interactions that drive amnion morphogenesis. In addition, integrative comparisons across humans, non-human primates and in vitro stem cell-based models reveal that stem cell-based models recapitulate various stages of amnion development, emphasizing the need for careful selection of model systems to accurately recapitulate in vivo amnion formation. Collectively, our findings provide a detailed view of amnion cellular composition and interactions, advancing our understanding of its developmental role and regenerative potential.
羊膜是支持胎儿发育的关键胚外结构，但其个体发生仍不清楚。在这里，我们使用单细胞转录组学技术，确定了妊娠早期人类羊膜中的主要细胞类型和亚型，大致分为上皮、间充质和巨噬细胞谱系。我们发现了上皮-间充质和上皮-免疫转变，突出了妊娠早期的动态重塑。我们的结果进一步揭示了关键的细胞间通讯途径，包括从间充质细胞到上皮细胞的BMP4信号传导和从巨噬细胞到间充质细胞的TGF-β信号传导，这表明驱动羊膜形态发生的协调相互作用。此外，对人类、非人灵长类动物和基于体外干细胞的模型的综合比较表明，基于干细胞的模型概括了羊膜发育的各个阶段，强调了需要仔细选择模型系统以准确概括体内羊膜形成的必要性。总的来说，我们的发现提供了羊膜细胞组成和相互作用的详细视图，推进了我们对其发育作用和再生潜力的理解。
