Human blastoids model blastocyst development and implantation – Nature

One week after fertilization, human embryos implant into the uterus. This event requires that the embryo forms a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid¹. Here we show that naive human pluripotent stem cells (PXGL hPSCs)² triply inhibited for the Hippo, TGF-β, and ERK pathways efficiently (>70%) form blastoids generating blastocyst-stage analogs of the 3 founding lineages (>97% trophectoderm, epiblast, and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis and we observe that the epiblast induces the maturation of the polar trophectoderm that consequently acquires the specific capacity to attach to hormonally-stimulated endometrial cells, as during implantation. Such a human blastoid is a faithful, scalable, and ethical model to explore human implantation and development^3,4.