Single-cell reconstruction of the early maternal–fetal interface in humans
Open accessAbstract
During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.
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CellPhoneDB analysis identified putative receptor-ligand interactions uniquely enriched between hepatocytes of specific zones and the cell types in close proximity to these zonated hepatocytes.
“Specifically, we focused this analysis only on receptor-ligand interactions that are uniquely enriched between hepatocytes of specific zones and the cell types in close proximity to these zonated hepatocytes (Fig. 3c, Supplementary Data 3).”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [31]
The Methods describe CellPhoneDB as a framework for identifying receptor–ligand interactions enriched between cell types. The ‘Cell communication predicted by CellPhoneDB’ section applies it to the maternal–fetal interface, not to zonated hepatocytes or nearby liver cell types. The hepatocyte-specific finding is therefore not supported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSingle-cell RNA sequencing identified two anatomically distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts in the synovial sub-lining, and FAPα+THY1− destructive fibroblasts in the synovial lining layer.
“scRNASeq identified two anatomically distinct fibroblast subsets within the FAPα+ population: FAPα+ thymus cell antigen (THY1)+ immune ‘effector’ fibroblasts located in the synovial sub-lining, and FAPα+THY1− ‘destructive’ fibroblasts restricted to the synovial lining layer.”
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Significant diversity and functional heterogeneity exist within the fibroblast population during organ fibrosis.
“Increasingly sophisticated experimental approaches have allowed discovery of significant diversity and functional heterogeneity within the fibroblast population during organ fibrosis22–25 .”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [23]
Deletion of FAPα+ fibroblasts suppresses inflammation and bone erosions in mouse models of resolving and persistent arthritis.
“deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed inflammation and bone erosions in mouse models of resolving and persistent arthritis”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [23]
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- Authors
- Vento-Tormo, R., Efremova, M., Botting, R. A., Turco, M. Y., Vento-Tormo, M., Meyer, K. B., Park, J.-E., Stephenson, E., Polański, K., Goncalves, A., Gardner, L., Holmqvist, S., Henriksson, J., Zou, A., Sharkey, A. M., Millar, B., Innes, B., Wood, L., Wilbrey-Clark, A., Payne, R. P., Ivarsson, M. A., Lisgo, S., Filby, A., Rowitch, D. H., Bulmer, J. N., Wright, G. J., Stubbington, M. J. T., Haniffa, M., Moffett, A., & Teichmann, S. A.
- Affiliations
- Wellcome Sanger Institute (GB)
- Newcastle University (GB)
- University of Cambridge (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- European Bioinformatics Institute (GB)
- Corresponding author
- Haniffa, Muzlifah
- Moffett, Ashley
- Teichmann, Sarah A.
- ORCID
- Efremova, Mirjana
- Botting, Rachel A.
- Turco, Margherita Y.
- Meyer, Kerstin B.
- Park, Jong-Eun
- Stephenson, Emily
- Polański, Krzysztof
- Gardner, Lucy
- Holmqvist, Staffan
- Henriksson, Johan
- Sharkey, Andrew M.
- Wilbrey-Clark, Anna
- Payne, Rebecca P.
- Ivarsson, Martin A.
- Filby, Andrew
- Rowitch, David H.
- Bulmer, Judith N.
- Wright, Gavin J.
- Stubbington, Michael J. T.
- Haniffa, Muzlifah
- Moffett, Ashley
- Teichmann, Sarah A.
- Venue
- Nature
- Published
- 2018-11-14
- Volume
- 563
- Issue
- 7731
- Pages
- 347-353
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7612850
- OpenAlex
- W2900144939
- Cited by
- 2,358
- References
- 74
- Citations by year
- 2026: 263 · 2025: 297 · 2024: 307 · 2023: 360 · 2022: 369 · 2021: 334 · 2020: 279 · 2019: 139 · 2018: 2
- FWCI
- 82.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (204721/Z/16/Z, #MR/R006237/1, 107931/Z/15/Z, 206194)
- Royal Society (DH160216)
- Medical Research Council (MC_PC_12009, MR/R006237/1, MR/P001092/1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- maternal-fetal interface, decidua, placenta, trophoblast, decidual natural killer cells, intercellular communication, ligand-receptor interactions, placentation, first trimester, perivascular cells, stromal cells, immunomodulation, preeclampsia, stillbirth, single-cell transcriptomics, cell type specificity
- MeSH terms
- Cell Communication, Cell Differentiation, Decidua, Female, Fetus, Humans, Killer Cells, Natural, Ligands, Placenta, Pregnancy, Trophoblasts, Stromal Cells, Sequence Analysis, RNA, RNA, Small Cytoplasmic, Histocompatibility, Maternal-Fetal, Single-Cell Analysis, Transcriptome
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