A Single-Cell Characterization of Human Post-implantation Embryos Cultured In Vitro Delineates Morphogenesis in Primary Syncytialization

We performed single-cell RNA sequencing (scRNA-seq) analysis of human post-implantation trophoblast cells. A hierarchical model was established, which was characterized by the sequential and stepwise development of two primitive cytotrophoblast cell (pCTB) subtypes after the trophectoderm (TE), two primitive syncytiotrophoblast (pSTB) subtypes, and migrative trophoblast cells (MTB). Further analysis characterized a new subtype of fusion-competent cells, which not only prepare for fusion to form primitive syncytiotrophoblast but also possess migration ability, which could be dual-function cells during implantation. Our work allows for reconstruction of sequential trophoblast cell transcriptional programs transition during implantation and provides a valuable resource to study pathologies in early pregnancy, such as recurrent implantation failure.