The role of Fosl1 in transdifferentiation of embryonic stem (ES) cells to trophoblast giant-like cells

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2016-11-30

Authors

Uprety, Nadima

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Abstract

During mammalian embryonic development, the first lineage commitment event gives rise to two distinct cell populations: the trophectoderm (TE) and the inner cell mass (ICM). The TE consists of outer cells of the blastocyst and ultimately forms the placenta while the ICM gives rise to all the embryonic tissues. Numerous transcription factors (TFs) guiding ICM differentiation into different embryonic tissues have been characterized. However, only a few TFs that are required for TE specification and differentiation have been identified, and much less is understood as to how these TFs interact with other TFs or with their chromosomal targets in order to drive cell fate towards TE lineage. Understanding TE development is crucial because cells in this lineage are required for proper embryo implantation in the uterus. Defects in TE lineage can cause early failure of pregnancy as well as other pregnancy related disorders such as preeclampsia and intrauterine growth restriction (IUGR). Here, we characterize the function of one of TE-specific TFs, Fosl1, which was previously suggested as having some roles in placental development. We utilized mouse embryonic stem (ES) cells (derived from ICM) and showed that ectopic expression of Fosl1 can transdifferentiate ES cells to trophoblast giant-like cells. We show that Fosl1 does so by directly binding and activating TE-specific genes and genes associated with epithelial-mesenchymal transition (EMT). Using mouse trophoblast stem (TS) cells, we also establish that Fosl1 is required for specification of TS cells to trophoblast giant cells (TGCs) subtype. Therefore, our results suggest that Fosl1 serves as an important mediator of cell fate conversion from ES cells to trophoblast giant-like cells and that Fosl1 is a critical regulator of TS cell differentiation.

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