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Epigenetic changes play a role in regulating the epithelial-mesenchymal transition in human trophoblast differentiation [Methylation array]

ABSTRACT: Epigenetic changes play a role in regulating the epithelial-mesenchymal transition in human trophoblast differentiation [Methylation array]

PROVIDER: PRJNA1080617 | ENA |

REPOSITORIES: ENA

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Epigenetic changes play a role in regulating the epithelial-mesenchymal transition in human trophoblast differentiation [Methylation array]

Project description:The phenotype of term, human placental extravillous trophoblast (EVT) reflects both the first trimester differentiation from villous cytotrophoblast (CTB) and later gestational changes, including the loss of proliferative and invasive capacity. Invasion abnormalities, as observed in preeclampsia and placenta accreta spectrum, are not usually diagnosed until the second or even third trimester of pregnancy. Characterization of the normal processes at term, including arrest of invasion is therefore crucial. In this report gene expression analysis demonstrates definitively the epithelial-mesenchymal transition (EMT) mechanism which underlies differentiation and provides a trophoblast-specific EMT signature. Methylation profiling shows that CTB, already hypomethylated relative to other somatic cells, show a further degree of hypomethylation in their transition to EVT. A small fraction of genes show both gain of methylation and changes in gene expression. Prominent are genes involved in the EMT such as the transcription factor RUNX1, loss of which leads to reduced migratory capacity in JEG3 trophoblast cells. Examination of these EMT genes leads us to suggest that the gains of methylation may assist in maintaining term EVT in a mesenchymal but non-invasive state.

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Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation

Project description:Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation

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Project description:Myostatin (MSTN) is a TGF-β superfamily member and was recently shown to be secreted and functioning in the placenta. In this study, we perfomed mRNA sequencing on control and MSTN-treated primary trophoblast cells to decipher the underlying molecular mechanisms involved in MSTN-induced human trophoblast cell invasion.

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Project description:Trophoblast epithelial-mesenchymal transition (EMT) in abnormally invasive placenta (AIP)

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MAP3K4/CBP Regulated H2B acetylation Controls Epithelial-Mesenchymal Transition in Trophoblast Stem Cells

Project description:Epithelial stem cells self-renew while maintaining multipotency, but the dependence of stem cell properties on maintenance of the epithelial phenotype is unclear. We previously showed that trophoblast stem (TS) cells lacking the protein kinase MAP3K4 maintain properties of both stemness and epithelial-mesenchymal transition (EMT). Here, we show that MAP3K4 controls the activity of the histone acetyltransferase CBP, and that acetylation of histone H2B by CBP is specifically required to maintain the epithelial phenotype. Combined loss of MAP3K4/CBP activity represses expression of epithelial genes and causes TS cells to undergo EMT while maintaining their self-renewal and multipotency properties. The expression profile of MAP3K4 deficient TS cells defines an H2B acetylation regulated gene signature that closely overlaps with that of human breast cancer cells. Taken together, our data define an epigenetic switch that maintains the epithelial phenotype in TS cells and reveal previously unrecognized genes potentially contributing to breast cancer. Three separate trophoblast stem (TS) cell conditions were compared to define the gene expression changes that occur with the induction of epithelial-mesenchymal transition (EMT) in TS cells. These conditions were TS cells differentiated for 4 days (T^Diff), TS cells differentiated for 4-days and isolated following invasion through Matrigel (T^Inv), and TS cells with an inactive MAP3K4 (TS^KI4). All conditions were normalized to wild-type control TS cells (TS^WT). T^Diff and T^Inv were analyzed in triplicate. TS^KI4 was analyzed in duplicate in two independent biological replicates.

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Project description:ZEB2, a master regulator of the epithelial-mesenchymal transition, mediates trophoblast differentiation

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Trophoblast epithelial-mesenchymal transition (EMT) in abnormally invasive placenta (AIP)

Project description:Comparison of genes associated with the EMT between cytotrophoblast cells (CTB) and extravillous trophoblast cells (EVT) from normal third trimester placenta and abnormally invasive placenta (AIP)

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