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Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells

ABSTRACT: Fosl1 transdifferentiate embryonic stem cells to differentiated trophoblast stem cells

PROVIDER: PRJNA390304 | ENA |

REPOSITORIES: ENA

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Transcriptome profiling of control and FOSL1 knockdown Rcho-1 trophoblast stem (TS) cells

Project description:In hemochorial placentation, trophoblast stem cells differentiate into multiple lineages to aquire specific functions, such as invasive and endocrine phenotype. FOSL1 has been identified as a key regulator for trophoblast differentiation. We used microarray to detail mechanisms underlying FOSL1 signaling pathway in trophoblast differentiation. 3 replicates of differentiated Rcho1 TS cells expressing control shRNA; 3 replicates of differentiated Rcho1 TS cells expressing Fosl1 shRNA

2015-06-30 | E-GEOD-68272 | biostudies-arrayexpress

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.

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

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Project description:Rcho-1 trophoblast stem cells can be maintained in a trophoblast stem cell state or induced to differentiate into trophoblast giant cells. During the differentiation process the PI3K pathway is constitutively activated. Microarray analysis of stem, differentiated and differentiated Rcho-1 trophoblast stem cells treated with the PI3K inhibitor LY294002.

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