A new study has advanced understanding of the processes and factors required for the formation of a blastocyst - a ball of cells that forms in early pregnancy. The study, led by researchers at the Institute of Genetics and Cancer and the University of Cambridge, captured specific cell lines that could be used to generate blastoids, the in vitro model for blastocysts. During the course of the study, the researchers also discovered that the generation of human blastoids is very much more straight-forward than mouse blastoids.The focus of the study was to culture primitive endoderm cells from mouse blastocysts into self-renewing, stable lines.Previous attempts by other labs to maintain these lines resulted in the cells gradually differentiating into more mature extraembryonic endoderm. Protein cocktail To combat differentiation, the team investigated proteins in the blastocysts' environment that support the primitive endoderm cells. Specifically, they found some success with a protein cocktail that encouraged these cells to self-renew, including higher levels of two specific integrins (proteins involved in cell adhesion and signalling).They experimented with hydrogel substrates that mimic the mechanical environment of blastocysts, and found a hydrogel with a specific stiffness of 3.5kPA was optimal. This environment, combined with a fine-tuned concentration of a growth factor (FGF4), allowed the cells to proliferate successfully over several passages. Our lines could be expanded under these optimised conditions for just long enough for sufficient expansion. When injected into host blastocysts, our cell lines contributed specifically to the primitive endoderm lineage, confirming their identity and potential utility for future experiments.Interestingly, during the course of this study, our colleagues discovered that generation of human blastoids is very much more straight-forward than mouse blastoids, since human naïve pluripotent embryonic stem cells exhibit the surprising capacity to differentiate into both trophectoderm and primitive endoderm, and self-organise into blastocyst-like structures using simple, reproducible protocols. Professor Jenny Nichols Group Leader, Institute of Genetics and Cancer Related links Read the paper in Development Jenny Nichols Research Group Tags 2026 This article was published on Friday 19 June 2026
