Characterization of cytotrophoblast cell population dynamics throughout pregnancy

To understand cytotrophoblast (CTB) dynamics during pregnancy, we constructed a single-cell RNA sequencing dataset profiling over 35,000 CTBs isolated from human placental tissues at various gestational stages. Our analysis revealed a robust set of transcripts defining distinct CTB subsets and their spatial relationships within the placenta. We identified a transit-amplifying primitive trophoblast population that may contribute to the CTB pool and found that CTBs located at the smooth chorion form a leak-tight epithelial layer that adapts to low oxygen environments without undergoing syncytialization. Additionally, our study suggests that CTB fate in the villous chorion may be influenced by interactions with the basal lamina, as indicated by a population of BCAM+ CTBs. This subset, isolated from term placental tissue, displayed progenitor capabilities in organoid cultures, supporting the hypothesis that BCAM+ CTBs maintain a progenitor role late in pregnancy.