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Generation of human blastocyst-like structures from pluripotent stem cells

ABSTRACT: Generation of human blastocyst-like structures from pluripotent stem cells

PROVIDER: PRJEB44768 | ENA |

REPOSITORIES: ENA

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Generation of human blastocyst-like structures from pluripotent stem cells

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Generation of Blastocyst-like Structures from Extended Pluripotent Stem Cells

Project description:A single mouse blastomere from until 8-cell embryo can generate an entire blastocyst. Whether blastomere-like extended pluripotent stem cells (EPS cells) retain a similar generative capacity remains unknown. Here, we established a 3D differentiation system that enabled the generation of blastocyst-like structures from EPS cells (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell lineage allocation. EPS-blastoids formation 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 somatic cells via cellular reprograming. EPS-blastoids provide a unique platform for studying early embryogenesis, and pave the way to generate viable synthetic embryos using cultured cells.

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Generation of human blastocyst-like structures from pluripotent stem cells

Project description:Due to ethical concerns and restricted access to human blastocysts, we lack a comprehensive understanding of early human embryogenesis. A reliable model system that can recapitulate early stages of human embryogenesis would help solve this problem.Here we report a robust three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids also exhibited the developmental potential to undergo post-implantation morphogenesis in vitro to form structures with a cellular composition and transcriptome signature similar to human embryos that had been cultured in vitro for 8 or 10 days. In conclusion, human EPS-blastoids provide a robust new experimental platform for studying early developmental stages of the human embryo.

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Generation of Blastocyst-like Structures from Extended Pluripotent Stem Cells (single-cell RNA-Seq)

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