Cumming School of Medicine
Syncytiotrophoblast formation is influenced by genes involved in lipid biology
Abstract
dc:description.abstractThe placenta develops during pregnancy to support the nutritional demands of the embryo. In the murine placenta, nutrient and waste exchange occurs in the labyrinth, the syncytiotrophoblast (SynT) cells are the key cell type of this region. Multinucleated SynT cells are formed through the process of trophoblast fusion involving a lipid- signalling event and dynamic membrane rearrangement. Defects altering the structure and abundance of SynT cells in the labyrinth are enriched in embryonic lethal mouse mutants. From these findings, we are interested in understanding the regulation of lipid-related genes in trophoblast fusion. This project aimed to explore the role of lipid biology in trophoblast fusion. Aim 1 focused on identifying genes required for SynT formation. Three candidate genes were proposed for a role in SynT formation through combined literature review, phenotype database information, and gene ontology analysis. Baiap2, Tmed2 and Pgap2 were selected for their roles in lipid-biology and the reported placental phenotypes of mutant mice. Next, knockout lines of the selected genes were established in trophoblast stem cells using CRISPR-Cas9. Aim 2 characterized the effect of each gene knockout on trophoblast differentiation, specifically any defects in differentiating into the SynT lineages. This was achieved through the assessment of lineage-specific marker gene expression by RT-qPCR. The Tmed2 KO was enriched for the SynT-I lineage, while the Pgap2 KO was deficient for the SynT-I population. Baiap2 KO clones were fate restricted to TGC, unable to form SynT cells. Aim 3 characterized trophoblast fusion in vitro. Anecdotally, cell seeding density has been reported to influence cell fusion. This hypothesis was systematically tested with three seeding densities, assessed at four time points. These experiments confirmed that increased seeding density causes increased cell fusion. Taken together these data present evidence for the importance of lipid-biology in trophoblast fusion. Tmed2 and Pgap2 are involved in GPI anchor biosynthesis, and the KO cells have specific phenotypes regarding SynT-I differentiation. The effects of seeding density indicate that the abundance of progenitor cells has a profound impact on trophoblast lineage differentiation, providing further insight into the process of SynT formation.
Degree
thesis:*- Name thesis:degree_name
- Master of Science (MSc)
- Discipline thesis:degree_discipline
- Medicine – Biochemistry and Molecular Biology
- Grantor dc:publisher.institution
- Cumming School of Medicine
- Year dc:date.issued
- 2026
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Apantaku, Ifeoluwa Olamide
- Advisor dc:contributor.advisor
-
- Hemberger, Myriam
- Committee members dc:contributor.committeemember
-
- McFarlane, Sarah
- Newton, Robert
Subjects
dc:subject × 6Rights
dc:rights- Statement dc:rights
-
- University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:ucalgary.scholaris.ca:1880/125316