Single-cell atlas of patient-derived trophoblast organoids (TO) in on-going pregnancies.

Trophoblast organoids (TOs) hold great promise for elucidating human placental development and function. By deriving TOs in on-going pregnancies using chorionic villus sampling (CVS), we established a platform to study trophoblast differentiation and function in early pregnancy, including pregnancies with different fetal genetic abnormalities. We addressed cellular heterogeneity of CVS-derived TOs by providing a single-cell transcriptomic atlas and show that CVS-TOs recapitulate key aspects of the human placenta, including syncytial fusion and hormone synthesis. This study demonstrates the utility of trophoblast organoids for investigating genetic defects in the placenta and describes an experimental platform for future personalized placental medicine approaches, including genotype-phenotype mapping. TOs derived from chorionic villi (10-14 weeks of gestation) were dissociated into single-cell suspensions and subsequently processed on the 10X Genomics Chromium Platform using the Next GEM Single Cell 3' Reagent kit (v3.1) with Dual Index Kit following the manufacturer's protocol.