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A spatially resolved timeline of the human maternal-fetal interface

Cite this dataset

Soon, Erin (2023). A spatially resolved timeline of the human maternal-fetal interface [Dataset]. Dryad.


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 remodeling (SAR). However, it remains a matter of debate which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here, we used a multiomic approach combining the strengths of spatial proteomics and transcriptomics to construct the first spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) and a 37-plex antibody panel to analyze ~500,000 cells and 588 arteries within intact decidua from 66 patients between 6-20 weeks of gestation, integrating this with coregistered transcriptomic 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 increasingly enriched and colocalized at later time points.  In contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting unique monotonic and biphasic trends.  Lastly, we developed an integrated model of SAR where invasion is accompanied by upregulation of pro-angiogenic, immunoregulatory EVT programs that promote interactions with vascular endothelium while avoiding activation of maternal immune cells.


Stanford University