Trophoblast organoids as a model for maternal–fetal interactions during human placentation
| العنوان: | Trophoblast organoids as a model for maternal–fetal interactions during human placentation |
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| المؤلفون: | Margherita Y. Turco, Michael Hollinshead, Russell S. Hamilton, Ridma C. Fernando, Steven G.E. Marsh, Malwina Prater, Laura Esposito, Stephen O'Rahilly, Graham J. Burton, Lucy Gardner, Frank Reimann, Andrew M. Sharkey, Ashley Moffett, Myriam Hemberger, Richard G. Kay, Fiona M. Gribble, Helen E. Skelton, A.J. McWhinnie |
| المصدر: | Nature. 564:263-267 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Multidisciplinary, Cytotrophoblast, Decidua, Placentation, Trophoblast, Biology, Cell biology, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Syncytiotrophoblast, Placenta, embryonic structures, medicine, Organoid, Blastocyst, reproductive and urinary physiology |
| الوصف: | The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries2. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria3. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G+ extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment. An in vitro system that generates three-dimensional cultures of extraembryonic fetal trophoblast cells that differentiate into the two main types of trophoblast can be used to study human placental development. |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6c563ed080aaf7e5f723b4c1ce4e2774 https://doi.org/10.1038/s41586-018-0753-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........6c563ed080aaf7e5f723b4c1ce4e2774 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
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