Citation

  • Authors: Zhang, S., Chen, T., Chen, N., Gao, D., Shi, B., Kong, S., West, R. C., Yuan, Y., Zhi, M., Wei, Q., Xiang, J., Mu, H., Yue, L., Lei, X., Wang, X., Zhong, L., Liang, H., Cao, S., Belmonte, J. C. I., Wang, H., Han, J.
  • Year: 2019
  • Journal: Nat Commun 10 496
  • Applications: in vitro / DNA / jetPRIME
  • Cell type: Trophoblast stem cells

Abstract

Spatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.

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