Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Institute for Informatics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Stem Cell. 2023 Sep 7;30(9):1148-1165.e7. doi: 10.1016/j.stem.2023.08.005.
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.
原始人类多能干细胞具有显著的自我组织能力,能够形成胚泡样结构(“胚泡”),模拟植入前胚胎中的谱系分离。然而,胚泡在多大程度上能够再现人类植入后发育的特征仍未得到探索。在这里,我们报告说,在厚的三维(3D)细胞外基质上培养的胚泡可以捕获早期植入后发育的特征,包括内胚层管腔形成、滋养层谱系的快速扩张和多样化,以及第 14 天的绒毛外滋养细胞的强烈侵袭。延长胚泡培养会导致原始条纹标记物 TBXT 的局部激活,并在第 21 天出现胚胎生殖层。我们还表明,WNT 信号的调节改变了植入后胚泡中内胚层和滋养层命运之间的平衡。这项工作表明,3D 培养的胚泡提供了一个从植入前到早期原肠胚形成阶段的连续和整合的人类胚胎和胚胎外发育的体外模型系统。
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