Transcriptomic analysis reveals differential gene expression, alternative splicing, and novel exons during mouse trophoblast stem cell differentiation

Abstract

Background: Differentiation of mouse trophoblast stem cells (TSCs) to trophoblast giant cells (TGCs) has been widely used as a model system to study placental development and function. While several differentially expressed genes, including regulators of TSC differentiation, have been identified, a comprehensive analysis of the global expression of genes and splice variants in the two cell types has not been reported. Results: Here, we report ~ 7800 differentially expressed genes in TGCs compared to TSCs which include regulators of the cell cycle, apoptosis, cytoskeleton, cell mobility, embryo implantation, metabolism, and various signaling pathways. We show that several mitotic proteins, including Aurora A kinase, were downregulated in TGCs and that the activity of Aurora A kinase is required for the maintenance of TSCs. We also identify hitherto undiscovered, cell-type specific alternative splicing events in 31 genes in the two cell types. Finally, we also report 19 novel exons in 12 genes which are expressed in both TSCs and TGCs. Conclusions: Overall, our results uncover several potential regulators of TSC differentiation and TGC function, thereby providing a valuable resource for developmental and molecular biologists interested in the study of stem cell differentiation and embryonic development.