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Spatial multiomics map of trophoblast development in early pregnancy

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, transfor...

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Autores principales: Arutyunyan, Anna, Roberts, Kenny, Troulé, Kevin, Wong, Frederick C. K., Sheridan, Megan A., Kats, Ilia, Garcia-Alonso, Luz, Velten, Britta, Hoo, Regina, Ruiz-Morales, Elias R., Sancho-Serra, Carmen, Shilts, Jarrod, Handfield, Louis-Francois, Marconato, Luca, Tuck, Elizabeth, Gardner, Lucy, Mazzeo, Cecilia Icoresi, Li, Qian, Kelava, Iva, Wright, Gavin J., Prigmore, Elena, Teichmann, Sarah A., Bayraktar, Omer Ali, Moffett, Ashley, Stegle, Oliver, Turco, Margherita Y., Vento-Tormo, Roser
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076224/
https://www.ncbi.nlm.nih.gov/pubmed/36991123
http://dx.doi.org/10.1038/s41586-023-05869-0
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author Arutyunyan, Anna
Roberts, Kenny
Troulé, Kevin
Wong, Frederick C. K.
Sheridan, Megan A.
Kats, Ilia
Garcia-Alonso, Luz
Velten, Britta
Hoo, Regina
Ruiz-Morales, Elias R.
Sancho-Serra, Carmen
Shilts, Jarrod
Handfield, Louis-Francois
Marconato, Luca
Tuck, Elizabeth
Gardner, Lucy
Mazzeo, Cecilia Icoresi
Li, Qian
Kelava, Iva
Wright, Gavin J.
Prigmore, Elena
Teichmann, Sarah A.
Bayraktar, Omer Ali
Moffett, Ashley
Stegle, Oliver
Turco, Margherita Y.
Vento-Tormo, Roser
author_facet Arutyunyan, Anna
Roberts, Kenny
Troulé, Kevin
Wong, Frederick C. K.
Sheridan, Megan A.
Kats, Ilia
Garcia-Alonso, Luz
Velten, Britta
Hoo, Regina
Ruiz-Morales, Elias R.
Sancho-Serra, Carmen
Shilts, Jarrod
Handfield, Louis-Francois
Marconato, Luca
Tuck, Elizabeth
Gardner, Lucy
Mazzeo, Cecilia Icoresi
Li, Qian
Kelava, Iva
Wright, Gavin J.
Prigmore, Elena
Teichmann, Sarah A.
Bayraktar, Omer Ali
Moffett, Ashley
Stegle, Oliver
Turco, Margherita Y.
Vento-Tormo, Roser
author_sort Arutyunyan, Anna
collection PubMed
description 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 vessels(1). Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia(2). 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 organoids(3,4) and trophoblast stem cells(5). 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.
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spelling pubmed-100762242023-04-07 Spatial multiomics map of trophoblast development in early pregnancy Arutyunyan, Anna Roberts, Kenny Troulé, Kevin Wong, Frederick C. K. Sheridan, Megan A. Kats, Ilia Garcia-Alonso, Luz Velten, Britta Hoo, Regina Ruiz-Morales, Elias R. Sancho-Serra, Carmen Shilts, Jarrod Handfield, Louis-Francois Marconato, Luca Tuck, Elizabeth Gardner, Lucy Mazzeo, Cecilia Icoresi Li, Qian Kelava, Iva Wright, Gavin J. Prigmore, Elena Teichmann, Sarah A. Bayraktar, Omer Ali Moffett, Ashley Stegle, Oliver Turco, Margherita Y. Vento-Tormo, Roser Nature Article 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 vessels(1). Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia(2). 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 organoids(3,4) and trophoblast stem cells(5). 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. Nature Publishing Group UK 2023-03-29 2023 /pmc/articles/PMC10076224/ /pubmed/36991123 http://dx.doi.org/10.1038/s41586-023-05869-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Arutyunyan, Anna
Roberts, Kenny
Troulé, Kevin
Wong, Frederick C. K.
Sheridan, Megan A.
Kats, Ilia
Garcia-Alonso, Luz
Velten, Britta
Hoo, Regina
Ruiz-Morales, Elias R.
Sancho-Serra, Carmen
Shilts, Jarrod
Handfield, Louis-Francois
Marconato, Luca
Tuck, Elizabeth
Gardner, Lucy
Mazzeo, Cecilia Icoresi
Li, Qian
Kelava, Iva
Wright, Gavin J.
Prigmore, Elena
Teichmann, Sarah A.
Bayraktar, Omer Ali
Moffett, Ashley
Stegle, Oliver
Turco, Margherita Y.
Vento-Tormo, Roser
Spatial multiomics map of trophoblast development in early pregnancy
title Spatial multiomics map of trophoblast development in early pregnancy
title_full Spatial multiomics map of trophoblast development in early pregnancy
title_fullStr Spatial multiomics map of trophoblast development in early pregnancy
title_full_unstemmed Spatial multiomics map of trophoblast development in early pregnancy
title_short Spatial multiomics map of trophoblast development in early pregnancy
title_sort spatial multiomics map of trophoblast development in early pregnancy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076224/
https://www.ncbi.nlm.nih.gov/pubmed/36991123
http://dx.doi.org/10.1038/s41586-023-05869-0
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