Single-cell dissection of cervix and placenta reveal both novel and overlapping cell types

Placental trophoblasts have been detected in cervical smears early in gestation, creating opportunities for non-invasive prenatal diagnosis. However, trophoblast isolation is limited by lack of a cell catalogue and molecular profile of cervical smears. To establish an atlas and explore the potential of single-cell RNA-sequencing to detect cervical trophoblasts, 10,539 single-cell transcriptomes from 12 non-invasive exocervical smears from pregnant women and 34,565 cells from six placentas were profiled. We uncovered a novel extravillous trophoblast cell subtype characterized by epithelial marker genes and reduced HLA-G expression. Integration of both cell atlases demonstrated surprisingly similar expression profiles between maternal epithelial cells and placental extravillous trophoblasts, indicating trophoblasts retained epithelial properties without an invasive mesenchymal phenotype. Differential expression analysis identified novel markers discriminating cervical and placental cell types. Using those markers for immunocytochemistry we demonstrate the frequency of exocervical trophoblast cells to be lower than reported.