Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Hartmann, T.
Transcriptome analysis of the fetal-maternal interface at single cell resolution in early pregnancy
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Feichtinger Julia
- Moser Gerit
- Altmetrics:
- Abstract:
- Purpose: Histiotrophic nutrition in early human pregnancy is enabled by fetal extravillous trophoblast cells (EVTs) invading and eroding the maternal uterine glands (the so-called endoglandular trophoblast invasion). This might be the missing piece of the puzzle explaining fetal alimentation during the first trimester of pregnancy. A lot of respective descriptive work supporting the concept of histiotrophic nutrition in humans is published, but it remains still unclear which intercellular signaling pathways are orchestrating the specific interactions between EVTs and uterine glands during early pregnancy. Therefore, this study aims to identify specific ligand-receptor interactions between EVTs and glandular epithelial cells (Epi) of the decidua, fostering our understanding of the cellular signaling behind endoglandular trophoblast invasion enabling histiotrophic nutrition. Methods: We performed a bioinformatics analysis of a publicly available dataset containing trophoblast invaded decidual tissue of the first trimester. In this study, we focused on the samples originating from decidual tissue. Therefore, we processed the data, performed batch effect correction by integrating the data, and identified and annotated the cell clusters of the decidual tissue. Finally, we inferred cell-cell communication in the fetal-maternal microenvironment by applying a ligand-receptor interaction analysis. Results: We were able to reproduce most of the findings that were previously published based on this publicly available dataset. For example, we also identified four subsets of decidual natural killer cells (dNKs) and inferred similar interactions between EVTs and immune cells in the decidua. This evaluated the data, which served as a basis for further research. Furthermore, we were able to improve our results by data integration, particularly the cell clustering in the decidual tissue. Importantly, our analysis revealed several ligand-receptor interactions between EVTs and Epis. Among them, LAMB3-DAG1 seems to be most promisingly involved in endoglandular trophoblast invasion. The data further showed cellular crosstalk between EVTs and Epis via CDH1-CDH1, VEGFA-VEGFR1, LAMB3-CD44, CXCL16-CXCR6 and others. Conclusion: The identified interaction of LAMB3-DAG1 could be crucial for guiding EVTs during their invasion into the uterine glands in early pregnancy. Further research, in particular immunohistochemical verification and mechanistic approaches of the predicted interaction are needed to confirm this hypothesis.