The Cellular Intricacies of the Human Placenta
Rare samples saved 35 years ago helped researchers map gene expression and cell differentiation in first trimester placentas.
Apart from possibly the great apes, no animal has a placenta quite like ours,1 which makes it difficult to study. But studying the placenta is critical since it plays a role in life-threatening pregnancy disorders such as pre-eclampsia. With this in mind, Ashley Moffett from the University of Cambridge saved samples from first trimester hysterectomies carried out as treatment for cervical cancer 35 years ago. Today, we vaccinate against a common viral cause for cervical cancer, so early pregnancy hysterectomies are extremely rare, making these samples precious.
“I wouldn’t let anyone near them because I knew, at some point, people would be able to actually do something [with them],” Moffett said. That point has arrived.
In collaboration with the Wellcome Sanger Institute, Moffett and her colleagues used these samples to map gene expression in the early placenta at the resolution of a single cell. Using spatial transcriptomics, single-cell RNA sequencing, and chromatin accessibility assays, they pinned down cell differentiation trajectories of the fetus-produced organ as it invades the uterus and transforms maternal arteries.2 “It’s an amazing effort,” commented Nardhy Gomez-Lopez, a maternal-fetal immunologist at Wayne State University, who was not involved in the study.
Moffett hopes that the map will help improve placenta models so that scientists can better understand diseases and test drugs. It has already showed that trophoblast organoids (self-assembled miniature placentas) reproduce the relevant cell differentiation, even though they do not reach full functionality, probably due to missing maternal signals.
The next step is to understand what happens in the second trimester where most of the diseases occur, said Gomez-Lopez, but securing samples will be hard as they depend on unusually late terminations. Any progress made, however, will benefit both those pregnant and their children, said Moffett. “What happens to you as a baby in utero affects the whole of the rest of your life. … It’s about the next generation.”