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Significance Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative trophoblasts, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated syncytiotrophoblast, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta.

Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta