2025-09-08 カリフォルニア工科大学 (Caltech)
Stem cell-based embryo models dividing.
Credit: Courtesy of M. Zernicka-Goetz
<関連情報>
- https://www.caltech.edu/about/news/stem-cellbased-embryo-models-reveal-pathway-to-understanding-fertility
- https://www.cell.com/developmental-cell/fulltext/S1534-5807(25)00504-0
環境研究のための効率的な幹細胞由来マウス胚モデル Efficient stem cell-derived mouse embryo models for environmental studies
Victoria Jorgensen ∙ Min Bao ∙ Sergi Junyent ∙ … ∙ Amanda Wu ∙ Matt Thomson ∙ Magdalena Zernicka-Goetz
Developmental Cell Published: August 28, 2025
DOI:https://doi.org/10.1016/j.devcel.2025.08.004
Highlights
- Aggregation of ESCs, TSCs, and inducible GATA4-ESCs builds mouse iGATA4-blastoids
- iGATA4-blastoids form with 80% efficiency and closely resemble E4.5 blastocysts
- Their modular design faithfully captures the cell proportions of natural embryos
- iGATA4-blastoids can be used in multiparametric screens with embryo-like phenotypes
Summary
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.
