Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures

Ronghui Li, Cuiqing Zhong, Yang Yu, Haisong Liu, Masahiro Sakurai, Leqian Yu, Zheying Min, Lei Shi, Yulei Wei, Yuta Takahashi, Hsin Kai Liao, Jie Qiao, Hongkui Deng, Estrella Nuñez-Delicado, Concepcion Rodriguez Esteban, Jun Wu, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

A single mouse blastomere from an embryo until the 8-cell stage can generate an entire blastocyst. Whether laboratory-cultured cells retain a similar generative capacity remains unknown. Starting from a single stem cell type, extended pluripotent stem (EPS) cells, we established a 3D differentiation system that enabled the generation of blastocyst-like structures (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell-lineage allocation and recapitulated key morphogenetic events during preimplantation and early postimplantation development in vitro. Upon transfer, some EPS-blastoids underwent implantation, induced decidualization, and generated live, albeit disorganized, tissues in utero. Single-cell and bulk RNA-sequencing analysis revealed that EPS-blastoids contained all three blastocyst cell lineages and shared transcriptional similarity with natural blastocysts. We also provide proof of concept that EPS-blastoids can be generated from adult cells via cellular reprogramming. EPS-blastoids provide a unique platform for studying early embryogenesis and pave the way to creating viable synthetic embryos by using cultured cells.

Original languageEnglish (US)
Pages (from-to)687-702.e18
JournalCell
Volume179
Issue number3
DOIs
StatePublished - Oct 17 2019

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Keywords

  • blastocyst
  • blastoids
  • EPS cells
  • EPS-blastoid
  • extended pluripotent stem cells
  • implantation
  • reprogramming
  • totipotent

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Li, R., Zhong, C., Yu, Y., Liu, H., Sakurai, M., Yu, L., Min, Z., Shi, L., Wei, Y., Takahashi, Y., Liao, H. K., Qiao, J., Deng, H., Nuñez-Delicado, E., Rodriguez Esteban, C., Wu, J., & Izpisua Belmonte, J. C. (2019). Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures. Cell, 179(3), 687-702.e18. https://doi.org/10.1016/j.cell.2019.09.029