Efficient stem cell-derived mouse embryo models for environmental studies
Year: 2025
Type: article
Abstract: Blastoids are stem cell-derived structures that mimic natural blastocysts by incorporating all three lineages: trophectoderm, epiblast, and primitive endoderm. However, current methods often yield incomplete structures that fail to cavitate or to form a proper primitive endoderm. To overcome these limitations, we develop a modular approach by aggregating three murine stem cell types: embryonic stem cells (ESCs), ESCs with inducible GATA4 expression (iG4-ESCs), and trophoblast stem cells (TSCs). This method yields cavitated blastocyst-like structures-termed iG4-blastoids-with approximately 80% efficiency. Single-cell RNA sequencing confirms their close resemblance to mature mouse blastocysts. Notably, culturing iG4-blastoids without FGF4 enhances specification of the invasive mural trophectoderm, and approximately 12% of structures undergo post-implantation-like morphogenesis in vitro. Using this model, we show that caffeine, alcohol, nicotine, and amino acid variations affect iG4-blastoids and natural embryos similarly, underscoring their utility as a robust model for investigating the impact of diverse environmental factors on embryogenesis.
Source: Developmental Cell
Authors: Victoria Jorgensen, Min Bao, Sergi Junyent, Christoph M. Häfelfinger, Laura Amaya, Zhaodi Liao, Brian A. Williams, Dong-Yuan Chen, Amanda Wu, Matt Thomson, Magdalena Zernicka-Goetz
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Human Frontier Science Program, Human Frontier Science Program, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Schweizerische Studienstiftung, National Institutes of Health, University of California, San Francisco, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China
OpenAlex ID: W4413814185