Spatial multiomics map of trophoblast development in early pregnancy

Anna Arutyunyan, Kenny Roberts, Kevin Troulé, Frederick C. K. Wong, Megan A. Sheridan, Ilia Kats, Luz Garcia-Alonso, Britta Velten, Regina Hoo, Elias R. Ruiz-Morales, Carmen Sancho-Serra, Jarrod Shilts, Louis-Francois Handfield, Luca Marconato, Elizabeth Tuck, Lucy Gardner, Cecilia Icoresi Mazzeo, Qian Li, Iva Kelava, Gavin J. Wright, Elena Prigmore, Sarah A. Teichmann, Omer Ali Bayraktar (), Ashley Moffett (), Oliver Stegle (), Margherita Y. Turco () and Roser Vento-Tormo ()
Additional contact information
Anna Arutyunyan: Wellcome Sanger Institute
Kenny Roberts: Wellcome Sanger Institute
Kevin Troulé: Wellcome Sanger Institute
Frederick C. K. Wong: Wellcome Sanger Institute
Megan A. Sheridan: University of Cambridge
Ilia Kats: German Cancer Research Center (DKFZ)
Luz Garcia-Alonso: Wellcome Sanger Institute
Britta Velten: Wellcome Sanger Institute
Regina Hoo: Wellcome Sanger Institute
Elias R. Ruiz-Morales: Wellcome Sanger Institute
Carmen Sancho-Serra: Wellcome Sanger Institute
Jarrod Shilts: Wellcome Sanger Institute
Louis-Francois Handfield: Wellcome Sanger Institute
Luca Marconato: German Cancer Research Center (DKFZ)
Elizabeth Tuck: Wellcome Sanger Institute
Lucy Gardner: University of Cambridge
Cecilia Icoresi Mazzeo: Wellcome Sanger Institute
Qian Li: University of Cambridge
Iva Kelava: Wellcome Sanger Institute
Gavin J. Wright: University of York
Elena Prigmore: Wellcome Sanger Institute
Sarah A. Teichmann: Wellcome Sanger Institute
Omer Ali Bayraktar: Wellcome Sanger Institute
Ashley Moffett: University of Cambridge
Oliver Stegle: Wellcome Sanger Institute
Margherita Y. Turco: University of Cambridge
Roser Vento-Tormo: Wellcome Sanger Institute

Nature, 2023, vol. 616, issue 7955, 143-151

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-023-05869-0

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