Trophoblast organoids for the investigation of placentation influences
2024
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland(1)
University of Cambridge, Cambridge, United Kingdom(2)
Wellcome Sanger Institute, Cambridge, United Kingdom(3)
University of Cambridge, Cambridge, United Kingdom(2)
Wellcome Sanger Institute, Cambridge, United Kingdom(3)
In humans, a balanced penetration of trophoblast cells into the endometrium, the decidua, is crucial for a successful pregnancy. There is evidence that this process is regulated by uterine natural killer cells (uNK cells), but it is unclear how they influence reproductive outcomes. Here, trophoblast organoids and primary tissue samples from pregnant women were used to determine how uNK cells influence placentation. By localising potential axes of interaction between trophoblasts and uNK cells using single cell transcriptomics and in vitro modelling of these interactions in organoids, a cytokine signal derived from uNK cells was identified that promotes trophoblast differentiation in the late phase of the invasive pathway. In addition, it influences transcriptional programmes involved in the regulation of blood flow, nutrients and inflammatory and adaptive immune responses, as well as gene signatures associated with pregnancy disorders such as pre-eclampsia. The results suggest mechanisms by which optimal immunological interactions between uNK cells and trophoblasts improve reproductive success.
Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy
Margherita Yayoi Turco(1), Qian Li(2), Ashley Moffett(2), Roser Vento-Tormo(3)
Added on: 03-26-2024
[1] https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00443-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590923004435%3Fshowall%3Dtrue#secsectitle0075[2] https://www.pcrm.org/news/ethical-science/lab-grown-mini-placentas-help-scientists-study-poorly-understood-pregnancy?emci=81cd97a0-5edd-ee11-85fb-002248223794&emdi=fcee0e40-f7de-ee11-85fb-002248223794&ceid=2015591
