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Developmental biology - Placenta
A Cell Map of Healthy Pregnancy Helps All
A new Human cell atlas reveals how the maternal immune system reacts to cells from the developing placenta...
In pregnancy, the embryo must be surrounded by a placenta in order to receive nutrients and oxygen transfused from the mother's blood system. The placenta grows along with the embryo, attaching to the lining of the uterus through a decidual layer of new tissue. It will be sloughed off with the placenta following baby's delivery.
As these invading cells - the trophoblast cells - are embryonic in origin, they have a genetic make-up different from the mother. The fetus by carrrying half the father's genes, is a "foreign" intruder. When trophoblast cells implant into the lining of the uterus, they are in fact invading the mother to reach her specialized blood vessels.
Thus, the decidua is a neutral zone existing between the mother and baby, where an immune compromise occurs between these two genetically different individuals. This compromise allows for safe and normal fetal development while still protecting mom from a "foreign" intruder.
"The formation of the decidua is vital for a successful pregnancy and our study has revealed completely new subtypes of cells within the decidua. Further clarification of what each of these cells do will help to understand how the maternal immune response helps achieve a successful pregnancy."
Ashley Moffett, Professor, Centre for Trophoblast Research, Department of Pathology, University of Cambridge, Cambridge, UK, and corresponding author.
The Human Cell Atlas documents how the maternal immune system makes modifications during early pregnancy to allow this arrangement. Such a cell map for healthy pregnancy helps us understand what goes wrong in miscarriage and pre-eclampsia when the neutral zone fails. Formerly called toxemia, preeclampsia is a condition marked by high blood pressure in women who never had high blood pressure before. It can be identified by high levels of protein in the mother's urine, often with swelling in her feet, legs, and hands.
Published in Nature, the map revealed new and unexpected cell states in the uterus and placenta, showing which genes are switched on in each cell.
This first Human Cell Atlas of early pregnancy, allowed researchers at the Wellcome Sanger Institute of Newcastle University and the University of Cambridge in the United Kingdom (UK) to map over 70,000 single cells along this decidual junction. It revealed which cells send signals to communicate with the mother's immune system.
"For the first time ever, we see which genes are active in each cell of the decidua and placenta, and discovered which of these could modify the maternal immune system."
Roser Vento-Tormo PhD, Wellcome Sanger Institute; Centre for Trophoblast Research,University of Cambridge, Cambridge, UK, and a first author on the paper.
Realizing that tumor cells may use similar mechanisms to evade the immune system to build a new blood supply for tumor growth, mapping the growth of the placenta has implications for the study of cancers which affect women, children - and men.
Abstract
During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-dicidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decicua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptivr immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentayion and reproductive success.
Authors
Roser Vento-Tormo, Mirjana Efremova, Rachel A. Botting, Margherita Y. Turco, Miquel Vento-Totmo, Kerstin B. Meyer, Jong-Eun Park, Emily Stephenson Krzystof Polanski, Angela Goncalves, Lucy Gardner, Staffan Holmqvist, Johan Hendriksson, Angela Zou, Andrew M. Sharkey, Ben Millar, Barbara Innes, Laura Wood, Anna Wilbrey-Clark, Rebecca P. Payne, Martin A. Ivarsson, Steve Lisgo, Andrew Filby, David H. Rowitch, Judith N. Bulmer, Gavin J. Wright, Michael J. T. Stubbington, Muzlifah Haniffa, Ashley Moffett, and Sarah A. Teichmann.
Acknowledgements
Selected websites:
Newcastle University
Key facts about the University of Newcastle are available at https://www.ncl.ac.uk/press/about/keyfacts/
About the University of Cambridge:
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 98 affiliates of the University have won the Nobel Prize. Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America. The University sits at the heart of the 'Cambridge cluster', which employs 60,000 people and has in excess of £12 billion in turnover generated annually by the 4,700 knowledge-intensive firms in and around the city. The city publishes 341 patents per 100,000 residents. http://www.cam.ac.uk
Wellcome Sanger Institute
The Wellcome Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute
Wellcome
Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk
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Nov 22, 2018 Fetal Timeline Maternal Timeline News News Archive
 Diagram illustrating decidual–placental interface in early pregnancy. DC, dendritic cells; dM, decidual macrophages; dS, decidual stromal cells; Endo, endothelial cells; Epi, epithelial glandular cells; F, fibroblasts; HB, Hofbauer cells; PV, perivascular cells; SCT, syncytiotrophoblast; VCT, villous cytotrophoblast; EVT, extravillous trophoblast. Single-cell reconstruction of early maternal–fetal interface.
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