Human blastoids model blastocyst development and implantation [scRNAseq]

Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form blastocyst models, which we termed blastoid. Here we show that naïve human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGFb, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation (>95%) analogs of the three founding lineages (trophoblast, epiblast, hypoblast), and in the sequential and timely manner of blastocysts. Blastoids spontaneously form an axis marked by maturation of the polar region, which acquires the potential to specifically attach to hormonally-stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development. Overall design: Blastoids and stem cells with various treatments