英国弗朗西斯·克里克研究所Silvia D.M. Santos团队在研究中取得进展。他们的最新研究提出了原肠胚后羊膜作为干细胞衍生的人类胚胎外发育模型。这一研究成果于2025年5月15日发表在国际顶尖学术期刊《细胞》上。
课题组提出了一个胚胎干细胞衍生的原肠胚后羊膜的3D模型，即原肠胚后羊膜（PGAs），它忠实地再现了受精后4周的胚胎外发育，密切模仿了人类羊膜囊的功能特征。PGAs自组织，形成羊膜和卵黄囊，并被胚外中胚层包围。利用PGAs，课题组发现GATA3是羊膜形成所必需的和充分的，并且一个自调节反馈回路控制羊膜的形成，由此胚胎外信号促进羊膜规范。PGA系统的可重复性和可扩展性，以及其精确的细胞、结构和功能完整性，为研究原肠胚形成之外的胚胎-羊膜相互作用开辟了途径，并为大规模药理和临床研究提供了理想的平台。
据了解，羊膜是哺乳动物胚胎中的胚胎外组织，被认为在怀孕期间提供重要的信号、结构和营养支持。尽管其至关重要，但由于缺乏准确的体外模型，对人类羊膜形成和功能的研究一直受到阻碍。
附：英文原文
Title: Post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development
Author: Borzo Gharibi, Oliver C.K. Inge, Irene Rodriguez-Hernandez, Paul C. Driscoll, Christelle Dubois, Ming Jiang, Michael Howell, J. Mark Skehel, James I. Macrae, Silvia D.M. Santos
Issue&Volume: 2025-05-15
Abstract: The amnion, an extra-embryonic tissue in mammalian embryos, is thought to provide crucial signaling, structural, and nutritional support during pregnancy. Despite its pivotal importance, studying human amnion formation and function has been hampered by the lack of accurate in vitro models. Here, we present an embryonic stem cell-derived 3D model of the post-gastrulation amnion, post-gastrulation amnioids (PGAs), that faithfully recapitulates extra-embryonic development up to 4 weeks post-fertilization, closely mimicking the functional traits of the human amniotic sac. PGAs self-organize, forming the amnion and the yolk sac, and are surrounded by the extra-embryonic mesoderm. Using PGAs, we show that GATA3 is required and sufficient for amniogenesis and that an autoregulatory feedback loop governs amnion formation, whereby extra-embryonic signals promote amnion specification. The reproducibility and scalability of the PGA system, with its precise cellular, structural, and functional integrity, opens avenues for investigating embryo-amnion interactions beyond gastrulation and offers an ideal platform for large-scale pharmacological and clinical studies.
DOI: 10.1016/j.cell.2025.04.025
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00458-1