Synthetic entities: blastocyst-like structures generated solely from stem cells
Sep. 6, 2018 17:30 - 18:30
DB Bldg. SeminarRoom A7F
Hubrecht Institute and MERLN Institute
The blastocyst, the early mammalian embryo, forms all embryonic and extra-embryonic tissues, including the placenta. It consists of a spherical thin-walled layer, the trophectoderm, that surrounds a fluid-filled cavity sheltering the embryonic cells.
From mouse blastocysts, both trophoblast and embryonic stem cell lines can be derived, which are in vitro analogues of the trophectoderm and embryonic compartments, respectively. Our lab showed that trophoblast and embryonic stem cells cooperate in vitro to form structures that morphologically and transcriptionally resemble E3.5 blastocysts ('blastoids'). Blastoids are permissive to the formation of primitive endoderm-like cells, the second extra-embryonic lineage, and implant upon in utero transfer.
Like blastocysts, blastoids form via inductive signals originating from the inner embryonic cells and driving outer trophectoderm development. The nature and function of these signals are largely unexplored. Genetically and physically uncoupling the embryonic and trophectoderm compartments, along with single cell transcriptomics, revealed an extensive list of inductive signals. We specifically show that the embryonic cells maintain trophoblast proliferation and self-renewal, while fine-tuning trophoblast epithelial morphogenesis. Altogether, these embryonic inductions are paramount to form a trophectoderm state that robustly implants and triggers a genuine decidualization in utero. Thus, at this stage, the nascent embryo fuels the development and implantation of the future placenta.
Our lab now investigates how synergies between the different compartmented cell types (epiblast, primitive endoderm, and trophoblast) regulate implantation and post-implantation development.
The blastoid is a unique and powerful tool that can be reproducibly generated in large numbers, finely tuned, contains all the cell types to form the conceptus, and implants in utero.
Rivron NC [corresponding author] et al. Blastocyst-like structures generated solely from stem cells. Nature (2018). doi:10.1038/s41586-018-0051-0.
Rivron NC. Formation of blastoids from mouse embryonic and trophoblast stem cells. Protocol Exchange (2018) doi:10.1038/protex.2018.051