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Nature. 2018 Nov;563(7731):347-353. doi: 10.1038/s41586-018-0698-6. Epub 2018 Nov 14.

Single-cell reconstruction of the early maternal-fetal interface in humans.

Author information

1
Wellcome Sanger Institute, Cambridge, UK.
2
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
3
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
4
Department of Pathology, University of Cambridge, Cambridge, UK.
5
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
6
YDEVS software development, Valencia, Spain.
7
German Cancer Research Center (DKFZ), Heidelberg, Germany.
8
Department of Paediatrics, Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
9
Human Developmental Biology Resource, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
10
Wellcome Sanger Institute, Cambridge, UK. m.a.haniffa@newcastle.ac.uk.
11
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. m.a.haniffa@newcastle.ac.uk.
12
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. m.a.haniffa@newcastle.ac.uk.
13
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. am485@cam.ac.uk.
14
Department of Pathology, University of Cambridge, Cambridge, UK. am485@cam.ac.uk.
15
Wellcome Sanger Institute, Cambridge, UK. st9@sanger.ac.uk.
16
Theory of Condensed Matter Group, The Cavendish Laboratory, University of Cambridge, Cambridge, UK. st9@sanger.ac.uk.
17
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK. st9@sanger.ac.uk.

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-decidual 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 decidua 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 adaptive 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 placentation and reproductive success.

PMID:
30429548
DOI:
10.1038/s41586-018-0698-6

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