美国华盛顿大学医学院Thorold W. Theunissen和Sabine Dietmann研究组，利用三维(3D)培养的囊胚模拟人类胚胎从着床前到早期原肠胚形成阶段。这一研究成果发表在2023年9月7日出版的国际学术期刊《细胞—干细胞》上。

他们报道了在厚的3D细胞外基质上培养的囊胚捕获了植入后早期发育的特征，包括外胚层放光形成，滋养细胞谱系的快速扩张和多样化，以及14天外胚层滋养细胞的强大侵袭。扩展囊胚培养导致原始条纹标记TBXT的局部激活，胚胎胚层在第21天出现。他们还表明，WNT信号的调节改变了着床后囊胚中外胚层和滋养层命运之间的平衡。

这项工作表明，3D培养的囊胚提供了从着床前到早期原肠胚形成阶段的人类胚胎和胚胎外发育的连续和完整的体外模型系统。

据悉，幼稚人类多能干细胞具有显著的自组织能力，能够形成囊胚样结构(“囊胚”)，模拟着床前胚胎的谱系分离。然而，囊胚在多大程度上可以概括人类植入后发育的定义特征仍未被探索。

附：英文原文

Title: 3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

Author: Rowan M. Karvas, Joseph E. Zemke, Syed Shahzaib Ali, Eric Upton, Eshan Sane, Laura A. Fischer, Chen Dong, Kyoung-mi Park, Fei Wang, Kibeom Park, Senyue Hao, Brian Chew, Brittany Meyer, Chao Zhou, Sabine Dietmann, Thorold W. Theunissen

Issue&Volume: 2023/09/07

Abstract: Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures (“blastoids”) that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day 21. We also show that the modulation of WNT signaling alters the balance between epiblast and trophoblast fates in post-implantation blastoids. This work demonstrates that 3D-cultured blastoids offer a continuous and integrated in vitro model system of human embryonic and extraembryonic development from pre-implantation to early gastrulation stages.

DOI: 10.1016/j.stem.2023.08.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00288-6