A spatially resolved timeline of the human maternal–fetal interface

Shirley Greenbaum (), Inna Averbukh, Erin Soon, Gabrielle Rizzuto, Alex Baranski, Noah F. Greenwald, Adam Kagel, Marc Bosse, Eleni G. Jaswa, Zumana Khair, Shirley Kwok, Shiri Warshawsky, Hadeesha Piyadasa, Mako Goldston, Angie Spence, Geneva Miller, Morgan Schwartz, Will Graf, David Valen, Virginia D. Winn, Travis Hollmann, Leeat Keren, Matt Rijn and Michael Angelo ()
Additional contact information
Shirley Greenbaum: Stanford University
Inna Averbukh: Stanford University
Erin Soon: Stanford University
Gabrielle Rizzuto: University of Californica San Francisco
Alex Baranski: Stanford University
Noah F. Greenwald: Stanford University
Adam Kagel: Stanford University
Marc Bosse: Stanford University
Eleni G. Jaswa: University of California San Francisco
Zumana Khair: Stanford University
Shirley Kwok: Stanford University
Shiri Warshawsky: Stanford University
Hadeesha Piyadasa: Stanford University
Mako Goldston: Stanford University
Angie Spence: Stanford University
Geneva Miller: California Institute of Technology
Morgan Schwartz: California Institute of Technology
Will Graf: California Institute of Technology
David Valen: California Institute of Technology
Virginia D. Winn: Stanford University
Travis Hollmann: Memorial Sloan Kettering Cancer Center
Leeat Keren: Weizmann Institute of Science
Matt Rijn: Stanford University
Michael Angelo: Stanford University

Nature, 2023, vol. 619, issue 7970, 595-605

Abstract: Abstract Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)1–3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal–fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06298-9 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:619:y:2023:i:7970:d:10.1038_s41586-023-06298-9

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06298-9

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().