Research on early human development has largely relied on excess embryos created through in vitro fertilization. Recent breakthroughs have allowed such embryos to be grown in vitro for periods approaching 14 days post-fertilization, but their utility for research is hampered by a limited supply, imperfect culture conditions and ethical concerns about overstepping the ‘14-day rule’. Embryonic stem cells could provide a useful alternative. Derived from the blastocyst, embryonic stem cells can differentiate into any cell type of the embryo proper, but — unlike the zygote — not the trophoblast or placenta. Previous work has demonstrated their potential for in vitro modelling of key developmental stages, such as formation of the blastocyst at day 5–6 post-fertilization. But mimicking the changes that occur after uterine implantation (at day 7–9) has proven especially challenging. A pair of papers in Nature report new strategies for achieving this.
Both studies generate models containing both embryonic and extraembryonic tissues. Pedroza, Gassaloglu et al. describe self-assembling aggregates of embryonic stem cells that recapitulate formation of the epiblast and hypoblast, but not trophoblast, with 78.3% efficiency. Hypoblast-like cells express genes promoting yolk sac endoderm formation by day 6. The method depends on using starting cells in an intermediate state between ground and primed pluripotency.
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