在胎盘形成过程中，胎盘细胞核合体滋养层细胞（CT细胞）分化成细胞质合体滋养层细胞（ST细胞）和绒外滋养层细胞（EVT细胞）。在胎盘中，通过转录复合物Yes-相关蛋白（YAP）/带有PDZ结合基序的转录增强因子（TAZ）-TEA结构域转录因子（TEAD）（YAP/TAZ-TEAD）活性，通过Hippo信号通路调节各种基因的表达。YAP/TAZ-TEAD活性受多种因素和信号的控制，如cAMP信号。cAMP信号被认为参与调节滋养层功能，但仍未完全了解。在这里，我们展示了人绒毛膜癌细胞系（BeWo细胞）中的cAMP刺激改变了YAP/TAZ-TEAD的表达和活性。YAP/TAZ-TEAD活性的抑制在未经cAMP刺激的情况下诱导了ST特异基因的表达，并且构成性活跃的YAP转导，即YAP-5SA，以TEAD依赖方式导致8Br-cAMP诱导的ST特异基因表达的抑制。我们还使用人胎盘干细胞（TS细胞）研究了YAP/TAZ-TEAD在维持CT细胞及其分化为ST和EVT细胞中的作用。YAP/TAZ-TEAD活性参与维持TS细胞的干性。诱导或抑制YAP/TAZ-TEAD活性会导致ST特异基因表达的显著变化。使用自发分化为类似ST的细胞的原始CT细胞研究了YAP-5SA转导的效应，并发现ST特异基因的表达被抑制。这些结果表明，在CT细胞分化为ST细胞的过程中，无论是否经过cAMP刺激，抑制YAP/TAZ-TEAD活性是必不可少的。© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD) activity. YAP/TAZ-TEAD activity is controlled by multiple factors and signaling, such as cAMP signaling. cAMP signaling is believed to be involved in the regulation of trophoblast function but is not yet fully understood. Here we showed that YAP/TAZ-TEAD expressions and their activities were altered by cAMP stimulation in BeWo cells, a human choriocarcinoma cell line. The repression of YAP/TAZ-TEAD activity induced the expression of ST-specific genes without cAMP stimulation, and transduction of constitutively active YAP, i.e. YAP-5SA, resulted in the repression of 8Br-cAMP-induced expressions of ST-specific genes in a TEAD-dependent manner. We also investigated the role of YAP/TAZ-TEAD in maintaining CT cells and their differentiation into ST and EVT cells using human trophoblast stem (TS) cells. YAP/TAZ-TEAD activity was involved in maintaining the stemness of TS cells. Induction or repression of YAP/TAZ-TEAD activity resulted in marked changes in the expression of ST-specific genes. Using primary CT cells, which spontaneously differentiate into ST-like cells, the effects of YAP-5SA transduction were investigated, and the expression of ST-specific genes was found to be repressed. These results indicate that the inhibition of YAP/TAZ-TEAD activity, with or without cAMP stimulation, is essential for the differentiation of CT cells into ST cells.© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.