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

Cell. 2019 Oct 17;179(3):687-702.e18. doi: 10.1016/j.cell.2019.09.029.


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.

Keywords: EPS cells; EPS-blastoid; blastocyst; blastoids; extended pluripotent stem cells; implantation; reprogramming; totipotent.

MeSH terms

  • Animals
  • Blastocyst / cytology*
  • Blastocyst / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Lineage*
  • Cells, Cultured
  • Cellular Reprogramming Techniques / methods
  • Embryo Implantation*
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / metabolism
  • Research Embryo Creation / methods*
  • Transcriptome