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The first study by Human Cell on early pregnancy in humans showed how cells in placental development affect the functioning of the mother's immune system. Researchers from the Wellcome Sanger Institute, the University of Newcastle and the University of Cambridge have used genomics and bioinformatics approaches to map more than 70,000 unique cells at the junction of the uterus and placenta. This revealed how cells talk to each other to change the immune response and allow pregnancy.
Posted in Nature, this work presents new and unexpected cellular states in the uterus and placenta, as well as the genes activated in each cell. The resulting information will help us understand what leads to a successful pregnancy and what can go wrong during a miscarriage or pre-eclampsia.
It can sometimes be difficult to maintain a healthy pregnancy, many women with miscarriages or stillbirth, and others with problems such as pre-eclampsia. Many of these problems have their roots in the first weeks of pregnancy, when the placenta is formed.
The fetus creates a placenta that surrounds it in the uterus to provide nutrients and oxygen. This is in contact with the mother, where it is implanted in the lining of the uterus, called decidua, to create a good blood supply to the placenta. Research on the interface between the mother and the fetus could help answer many vital questions, including changing the mother's immune system to allow the mother and the developing fetus to coexist. However, until now, this area has not been well studied.
To understand this area, researchers studied more than 70,000 individual cells from first trimester pregnancies. Using single-cell RNA and DNA sequencing, they identified maternal and fetal cells in the decidua and placenta, and showed how these cells interacted with each other. They discovered that fetal and maternal cells used signals to talk to each other, and this conversation allowed the maternal immune system to support fetal growth.
Dr. Roser Vento-Tormo, lead author of the Wellcome Sanger Institute article, said, "For the first time in our lives, we have been able to determine which genes are active in each cell of the decidus and placenta. have discovered which of these could alter the maternal immune system Fetal cells in the placenta communicate with the mother's immune cells to ensure proper placement of placenta implants, allowing the fetus to develop and develop normally . "
Using microscopy-based methods, the researchers were also able to locate the new cell states in the different layers of the decidua. They saw how biological blocks of the placenta – called trophoblastic cells – invaded the lining of the mother's uterus and caused a change in tissue structure, thus creating a blood supply for the developing fetus.
Professor Muzlifah Haniffa, corresponding author of Newcastle University, said: "This study was only possible thanks to the human developmental biology resource, which provides tissues enabling research to understand human development in order to To improve our health, our single-cell study showed us the exact cell composition of the decidua and placenta for the first time and how the cells of the placenta and uterine development communicate. It has enormous implications for understanding what happens during a normal pregnancy and for studying what can go wrong during eclampsia and miscarriage. "
Professor Ashley Moffett, corresponding author of the University of Cambridge, said: "The formation of the deciduous is essential to the success of pregnancy and our study has revealed new subtypes of cells in the deciduous. the mother's immune system contributes to the success of the pregnancy. "
Understanding this area also has implications for the study of cancers. Tumor cells can use similar mechanisms to evade the immune system and extract a new blood supply to provide nutrients and oxygen for tumor growth.
Sarah Teichmann, author corresponding to the paper of the Wellcome Sanger Institute and co-chair of the organization's committee on the human cell atlas initiative, said: "This first atlas of human cells on early pregnancy provides us with a baseline map of this vital initial phase, which will transform our understanding of healthy development and help us understand how placental and maternal cells communicate to support pregnancy, which will lead to a better understanding of pregnancy disorders and could also help understand the pathways that cancer cells exploit. "
Explore further:
Mimic the human placental barrier to better understand the dynamic organ
More information:
Roser Vento-Tormo et al, Monocellular reconstruction of the early mother-to-fetus interface in humans, Nature (2018). DOI: 10.1038 / s41586-018-0698-6
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