S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1

Abstract

Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired β-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.

Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway

“…After being dissected and minced into small pieces, they were washed in PBS and enzymatically digested three times with a mixture containing TrypLE and Accumax for 20 min at 37 • C. The EasySep phycoerythrin (PE)-positive selection kit was used to immunomagnetically purify the cytotrophoblasts (CTBs). The selected cells then were seeded into 6-well plates precoated with collagen IV, and sustained and cultured with TS media [6] (Supplementary Figure S4). CTB cells were passaged at about 90% confluency.…”

“…Cytotrophoblast (CTB) progenitors can give rise to cells (EVTs) that invade the uterus and vasculature or generate multinuclear syncytiotrophoblasts (STBs) that form on the surface of the chorionic villi during the first trimester of human gestation [4,5]. Notably, human trophoblast stem (TS) cells, which were successfully derived from human blastocysts (TS blast ) or cytotrophoblast (TS CT ) cells in 2018, have been proved to be meritorious in vitro models for the characteristic analysis of human trophoblast cells based on their similar transcriptome to the primary trophoblasts [3,6].…”