Atlas of amnion development during the first trimester of human pregnancy
Creators
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1.
California Institute of Technology
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2.
Wellcome Sanger Institute
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3.
University of Cambridge
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4.
Great Ormond Street Hospital
Abstract
The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial–mesenchymal and epithelial–immune transitions, highlighting dynamic remodelling during early pregnancy. Our results further revealed key intercellular communication pathways, including BMP4 signalling from mesenchymal to epithelial cells and TGF-β signalling from macrophages to mesenchymal cells, suggesting coordinated interactions that drive amnion morphogenesis. In addition, integrative comparisons across humans, non-human primates and in vitro stem cell-based models reveal that stem cell-based models recapitulate various stages of amnion development, emphasizing the need for careful selection of model systems to accurately recapitulate in vivo amnion formation. Collectively, our findings provide a detailed view of amnion cellular composition and interactions, advancing our understanding of its developmental role and regenerative potential.
Copyright and License
© 2025, The Author(s). This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Acknowledgement
We thank members of the Zernicka-Goetz lab and A. Andersen from Life Science Editors for their helpful comments; M. Shahbazi and B. Weatherbee for their assistance with accessing the amnion samples. This work was founded by Wellcome Trust grants (098287/Z/12/Z to M.Z.-G. and 220540/Z/20/A to R.V.-T.), NOMIS Foundation Award (M.Z.-G.) and Open Philanthropy grant (M.Z.-G.). C.W.G. was supported by the Leverhulme Trust.
Data Availability
Sequencing data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE260715. Previously published human CS7 embryo data were downloaded from Array Express (E-MTAB-9388). Monkey CS8_CS11 data were obtained from GEO under accession number GSE193007. Stem cell-derived model data were downloaded from GSE179309, GSE205611 and GSE134571. The human reference genome (GRCh38/hg38) used for alignment was downloaded from the 10x Genomics website (https://cf.10xgenomics.com/supp/cell-exp/refdata-gex-GRCh38-2020-A.tar.gz). Source data are provided with this paper. All other data supporting the findings of this study are available from the corresponding author on reasonable request. Source data are provided with this paper.
Supplemental Material
- Supplementary Table 1. Marker genes of the ten Seurat clusters. S
- upplementary Table 2. Gene expression along pseudotime.
- Supplementary Table 3. Cell–cell interactions among amniotic cells.
- Supplementary Table 4. Differentially expressed gene modules.
- Supplementary Table 5. Antibodies and primers.
Contributions
Samples were collected by N.S. and K.M. Data analyses were conducted by W.H., histology by C.W.G. and immunostaining by H.M.S. The project was conceptualized by M.Z.-G. The paper was written by W.H., with the help of M.Z.-G., R.V.-T. and C.W.G. Single-cell sequencing was performed by C.S.-S. and R.V.-T.
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Additional details
Related works
- Describes
- Journal Article: https://rdcu.be/ewSYF (ReadCube)
Funding
- Wellcome Trust
- (098287/Z/12/Z) (MZG)
- Wellcome Trust
- 220540/Z/20/A
- Open Philanthropy Project
- Leverhulme Trust
- Nomis Foundation