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Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE100000 | GEO | 2018/04/25

REPOSITORIES: GEO

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Fosl1 overexpression directly activates trophoblast-specific gene expression programs in embryonic stem cells.

Project description:During early development in placental mammals, proper trophoblast lineage development is essential for implantation and placentation. Defects in this lineage can cause early pregnancy failures and other pregnancy disorders. However, transcription factors controlling trophoblast development remain poorly understood. Here, we utilize Fosl1, previously implicated in trophoblast giant cell development as a member of the AP-1 complex, to trans-differentiate embryonic stem (ES) cells to trophoblast lineage-like cells. We first show that the ectopic expression of Fosl1 is sufficient to induce trophoblast-specific gene expression programs in ES cells. Surprisingly, we find that this transcriptional reprogramming occurs independently of changes in levels of ES cell core factors during the cell fate change. This suggests that Fosl1 acts in a novel way to orchestrate the ES to trophoblast cell fate conversion compared to previously known reprogramming factors. Mapping of Fosl1 targets reveals that Fosl1 directly activates TE lineage-specific genes as a pioneer factor. Our work suggests Fosl1 may be used to reprogram ES cells into differentiated cell types in trophoblast lineage, which not only enhances our knowledge of global trophoblast gene regulation but also may provide a future therapeutic tool for generating induced trophoblast cells from patient-derived pluripotent stem cells.

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Neural differentiated mouse embryonic stem cells (mESCs) under exposure to sodium valproate and sodium arsenite

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells (RNA-seq)

Project description: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 trophectoderm development is crucial because cells in this lineage are required for proper embryo implantation in the uterus. Defects in this 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 TF, Fosl1, which was previously suggested as having some role 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 differentiated TS cells (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, we postulate that Fosl1 is a key regulator of TS cell differentiation.

2018-04-25 | GSE99984 | GEO

Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells. (ChIP-seq)

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Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells

Project description:Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells

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EZH2-RNA interactions in embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Modulation of HDAC activity directly reprogramme embryonic stem cell to trophoblast stem cell

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