Journal
CELL
Volume 179, Issue 3, Pages 687-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.09.029
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Funding
- Larry L. Hillblom Foundation
- Paul F. Glenn Foundation
- Salk Women & Science Special Award
- National Key R&D Program of China [2016YFC1000601]
- Hamon Center for Regenerative Science Medicine
- G. Harold and Leila Y. Mathers Charitable Foundation
- Moxie Foundation
- Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]
- Hewitt Foundation
- NIH [5 DP1 DK113616]
- Universidad Catolica San Antonio de Murcia
- Cancer Prevention & Research Institute of Texas (CPRIT)
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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.
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