Embryonic quality control after implantation with lineage-specific elimination of aneuploid cells

Here we define how this surveillance operates after implantation using an integrated, three-lineage stem cell–derived embryo model that recapitulates the epiblast (EPI), visceral endoderm (VE), and extraembryonic ectoderm (ExE). Seeding of aneuploid cells into each lineage independently revealed lineage-specific fates: aneuploid cells were selectively depleted from EPI and VE but persisted within ExE.

Live imaging captured their removal by apoptosis or physical extrusion. Single-cell RNA sequencing showed p53 activation and Myc repression in aneuploid cells, and pathway perturbations modulated their clearance, confirming causality. Together, these findings demonstrate a post-implantation, lineage-restricted quality-control program that eliminates aneuploid cells from the embryo proper while permitting extraembryonic tolerance.