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Spatial multiomics map of trophoblast development in early pregnancy.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Troulé, Kevin 
Wong, Frederick CK 

Abstract

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal-fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell-cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.

Description

Keywords

Female, Humans, Pregnancy, Cell Movement, Multiomics, Placenta, Pregnancy Trimester, First, Trophoblasts, Decidua, Maternal-Fetal Relations, Single-Cell Analysis, Myometrium, Cell Differentiation, Organoids, Stem Cells, Transcriptome, Transcription Factors, Cell Communication

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

616

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (063980/Z/01/Z)
Wellcome Trust (200841/Z/16/Z)
European Commission Horizon 2020 (H2020) ERC (853546)