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- W2334691623 abstract "Abnormal development of invasive trophoblasts has been implicated in the pathogenesis of human pregnancy diseases such as pre-eclampsia. However, critical signalling pathways controlling formation and differentiation of these cells have been poorly elucidated. Here ,w e provide evidence that the canonical Notch pathway, operating through Notch-dependent activation of its key regulatory transcription factor RBPJk, controls proliferation and differentiation in villous explant cultures and primary trophoblasts of early pregnancy. Immunofluorescence of first trimester placental tissue revealed expression of RBPJk and its co-activators, the MAML proteins, in nuclei of proliferative cell column tro- phoblasts (CCT) and differentiated, extravillous trophoblasts (EVTs). However, RBPJk expression, transcript levels of the Notch target gene HES1 and activity of a Notch/RBPJk-dependent luciferase reporter decreased during in vitro differentiation of primary cytotrophoblasts on fibro- nectin. Silencing of RBPJk using silencing RNAs (siRNAs) increased proliferation of CCTs in floating villous explant cultures analysed by outgrowth and BrdU labelling. Similarly, down-regulation of the transcription factor enhanced BrdU incorporation in isolated primary cultures. However, motility of these cells was not affected. In addition, gene silencing of RBPJk increased cyclin D1 expression in the two trophoblast model systems as well as markers of the differentiated, EVT, i.e. integrin a1, ADAM12 and T-cell factor 4. In summary, the data suggest that Notch- dependent RBPJk activity could be required for balanced rates of trophoblast proliferation and differentiation in human placental anchoring villi preventing exaggerated trophoblast overgrowth as well as premature formation of EVTs." @default.
- W2334691623 created "2016-06-24" @default.
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- W2334691623 date "2014-09-01" @default.
- W2334691623 modified "2023-09-23" @default.
- W2334691623 title "Notch-dependent RBPJκ restrains proliferation of human cytotrophoblasts and their differentiation into extravillous trophoblasts" @default.
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- W2334691623 doi "https://doi.org/10.1016/j.placenta.2014.06.335" @default.
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