Tuesday , January 26 2021

First Cellular Map to Prevent Pregnancy Complications – Tips



Spanish researchers participated in the publication of a complete and detailed cellular atlas of the interface between mother and fetus during the first trimester of pregnancy

During early human pregnancy, the uterine mucosa is transformed into deciduous, in which the fetal placenta is implanted and where the cells of the placental trophoblast are mixed and communicate with the maternal cells. The interactions Deciduous trophoblastic Underlying common diseases of pregnancy, including preeclampsia and fetal death. Here we present the transcriptome of approximately 70,000 individual cells from first trimester placentas with paired maternal blood and deciduous cells. The cell composition of human decidua reveals subsets of perivascular and stromal cells that are located in different deciduous layers. Exist three major subgroups of natural deciduous killer cells that have distinct immunomodulatory and chemokine profiles. We have developed a pool of ligand-receptor complexes and a statistical tool to predict the specificity of the cell-cell communication type through these molecular interactions. Our data identifies many regulatory interactions which avoid harmful innate or adaptive immune responses in this environment. Our unicellular atlas of the maternal-fetal interface reveals the cellular organization of the decidua and the placenta, and the interactions that are critical for placentation and reproductive success.

Scientists from the Wellcome Sanger Institute, the University of Newcastle and the University of Cambridge (UK) publish this week on the cover of the journal Nature the most detailed cellular map to date of the zone of contact between a mother and her future child. This atlas of cellular composition points out the possible keys to avoid the most common initial problems and achieve a successful pregnancy without complications.

Researchers, including the Spanish brothers Roser and Miquel Vento-Tormo, have mapped more than 70,000 transcriptomes (transcript DNA) of healthy cells collected between weeks 6 and 14 of pregnancy, thanks to complex bioinformatics and genomic techniques.

"The idea was to understand the mechanisms that occur in the first trimester of an uncomplicated pregnancy, so we created a reference map of all cells and their interactions to compare the differences between a healthy pregnancy and one that presents problems in the future," explains Roser Vento-Tormo, from the Wellcome Sanger Institute, to SINC.

"We found out which genes modify maternal immunity and allow proper development of the fetus," explains Roser Vento.

The analysis focuses on the first trimester, as it is a crucial moment that determines the survival of the embryo (and subsequent fetus). During these first weeks, placental fetal cells – which interact with those of the mother to modify her immune response – are formed, which try to avoid a rejection situation.

Thanks to them, the embryo is able to adhere to the uterus in the decidua, which is the innermost layer of the pregnant uterus that thickens to favor implantation. In addition, it serves as a way to feed and oxygenate the fetus over the next few months.

"For the first time in history we were able to see which genes are active in the cells that make up the decidua and the placenta, finding out which ones modify the maternal immune system and allow the correct development of the fetus," says Vento.

Fewer complications

The chances of suffering complications during pregnancy are greatest in the first few weeks, when the fetus is not yet consolidated. In fact, two of three miscarriages happen spontaneously during the first trimester.

Vento clarifies that, at the moment, the study focused only on understanding a healthy pregnancy. However, "in the future, we will be able to predict if there is any kind of change in early pregnancy by analyzing patient samples."

Muzlifah Haniffa, a researcher at the University of Newcastle, says these results "will have important implications for better understanding what happens when a pregnant woman suffers from preeclampsia or even when a miscarriage occurs."

In the future, experts will be able to predict if there is any kind of change early in a pregnancy

For experts, this finding will also have a major impact on cancer research since it is known that tumor cells use similar mechanisms to escape the immune system and nourish themselves with blood flow and increase in size.

A database open access

The results were obtained thanks to the creation of a tool developed in collaboration with Miquel Vento-Tormo and his team from the Spanish software development company YDEVS.

This database, called CellPhoneDB, collects information about molecules and their interactions, and predicts the most likely cellular interactions. According to Roser Vento, "this tool can be applied to any fabric. Together with my brother Miquel, we make it accessible to all".

Cellular map of the human body

This study is part of the Human Cell Atlas initiative, an international consortium led by Sara Teichmann, one of the leading supervisory authorities of this publication and also a researcher at the Wellcome Sanger Institute.

"With this initiative, we intend to make a complete reference map of all human cells to better diagnose diseases," Wind concludes.


Bibliographic reference:

R. Vento-Tormo et al. "Single-cell reconstruction of the early maternal-fetal interface in humans", NatureNovember 2018: https://www.nature.com/articles/s41586-018-0698-6


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