The first Human Cell Atlas study of early pregnancy in humans has shown how cells from the developing placenta affect the function of the maternal immune system. For the study, the scientists used genomic and bioinformatic approaches to map over 70,000 single cells at the junction of the uterus and placenta. Published in Nature, this work describes new and unexpected cell states in both the uterus and the placenta. It also describes which genes are switched on in each cell and how the cells communicate with each other.
"This first Human Cell Atlas of early pregnancy gives us a reference map of this vital initial phase of development,” says Dr. Sarah Teichmann of the Wellcome Sanger Institute. “It will transform our understanding of healthy development and is helping us understand how the placental and maternal cells communicate with each other to support pregnancy. This will shed light on disorders of pregnancy, and could also help understand pathways that cancer cells exploit."
The fetus creates a placenta to surround it in the uterus and provide nutrients and oxygen. The placenta eventually implants into the lining of the uterus, known as the decidua. Research on the interface between mother and fetus could help answer many vital questions—including how the mother's immune system is modified to allow both mother and the developing fetus to coexist.
To understand this particular question, researchers studied more than 70,000 single cells from first-trimester pregnancies. Using single-cell RNA and DNA sequencing, they identified maternal and fetal cells in the decidua and placenta and found how these cells interacted. They discovered that the fetal and maternal cells were using signals to talk to each other and that this conversation enabled the maternal immune system to support fetal growth.
Using microscopy-based methods, the researchers were also able to pinpoint the location of new cell states in the different layers of the decidua. They saw how the biological blocks of the placenta—called trophoblast cells—invade into the lining of the mother's uterus and cause the tissue to change structure, creating the blood supply for the developing fetus.
“The formation of the decidua is vital for a successful pregnancy,” says Dr. Ashley Moffett of Cambridge University, “and our study has revealed completely new subtypes of cells within the decidua.”