Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface
Abstract The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55597-w |
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| author | Dafina M. Angelova Aleksandra Tsolova Malwina Prater Noura Ballasy Wendi Bacon Russell S. Hamilton Danielle Blackwell Ziyi Yu Xin Li Xin Liu Myriam Hemberger D. Stephen Charnock-Jones |
| author_facet | Dafina M. Angelova Aleksandra Tsolova Malwina Prater Noura Ballasy Wendi Bacon Russell S. Hamilton Danielle Blackwell Ziyi Yu Xin Li Xin Liu Myriam Hemberger D. Stephen Charnock-Jones |
| author_sort | Dafina M. Angelova |
| collection | DOAJ |
| description | Abstract The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points. We show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the Syncytiotrophoblast-I lineage, initially share similar trajectories. Importantly, our functional analysis of one such lineage precursor marker, CXADR, demonstrates that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease. |
| format | Article |
| id | doaj-art-ee46e1fc0a5f442c8ffa6625971a6150 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ee46e1fc0a5f442c8ffa6625971a61502025-01-05T12:37:24ZengNature PortfolioNature Communications2041-17232025-01-0116112210.1038/s41467-024-55597-wSingle-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surfaceDafina M. Angelova0Aleksandra Tsolova1Malwina Prater2Noura Ballasy3Wendi Bacon4Russell S. Hamilton5Danielle Blackwell6Ziyi Yu7Xin Li8Xin Liu9Myriam Hemberger10D. Stephen Charnock-Jones11Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research CentreDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NWLoke Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of CambridgeDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NWLoke Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of CambridgeLoke Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of CambridgeDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NWCollege of Chemical Engineering, Nanjing Tech UniversitySphere Fluidics Ltd., Building One, Granta Centre, Granta Park, Great AbingtonSphere Fluidics Ltd., Building One, Granta Centre, Granta Park, Great AbingtonDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NWDepartment of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research CentreAbstract The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points. We show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the Syncytiotrophoblast-I lineage, initially share similar trajectories. Importantly, our functional analysis of one such lineage precursor marker, CXADR, demonstrates that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease.https://doi.org/10.1038/s41467-024-55597-w |
| spellingShingle | Dafina M. Angelova Aleksandra Tsolova Malwina Prater Noura Ballasy Wendi Bacon Russell S. Hamilton Danielle Blackwell Ziyi Yu Xin Li Xin Liu Myriam Hemberger D. Stephen Charnock-Jones Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface Nature Communications |
| title | Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface |
| title_full | Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface |
| title_fullStr | Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface |
| title_full_unstemmed | Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface |
| title_short | Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface |
| title_sort | single cell rna sequencing identifies cxadr as a fate determinant of the placental exchange surface |
| url | https://doi.org/10.1038/s41467-024-55597-w |
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