ZBED1 Regulates Genes Important for Multiple Biological Processes of the Placenta

Abstract

The transcription factor ZBED1 is highly expressed in trophoblast cells, but its functions in the processes of trophoblast and placental biology remain elusive. Here, we characterized the role of ZBED1 in trophoblast cell differentiation using an in vitro BeWo cell model. We demonstrate that ZBED1 is enhanced in its expression early after forskolin-induced differentiation of BeWo cells and regulates many of the genes that are differentially expressed as an effect of forskolin treatment. Specifically, genes encoding markers for the differentiation of cytotrophoblast into syncytiotrophoblast and factors essential for trophoblast cell fusion and invasion were negatively regulated by ZBED1, indicating that ZBED1 might be important for maintaining a steady pool of cytotrophoblast cells. In addition, ZBED1 affected genes involved in the regulation of trophoblast cell survival and apoptosis, in agreement with the observed increase in apoptosis upon knockdown of ZBED1 in forskolin-treated BeWo cells. In addition, genes implicated in the differentiation, recruitment, and function of innate immune cells by the placenta were affected by ZBED1, further suggesting a role for this protein in the regulation of maternal immune tolerance. In conclusion, our study implicates ZBED1 in major biological processes of placental biology.

Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta

“…Intriguingly, ZBED1 does regulate proliferation ( 103 ) and is expressed in human placenta, with higher levels in postmitotic STB expression than CTB ( 104 ). Recently, partial knockdown of ZBED1 in the BeWo trophoblastic cell model was reported to increase apoptosis of syncytiated cells ( 105 ), which is consistent with the STB defect reported herein.…”

The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development

“…An SNP highly associated with early puberty of a tropical species of cattle (Bos indicus) was located most proximally to the RELL1 gene [97], and RELL1 was associated with prolificacy in goats in a separate study [98], further supporting a role of RELL1 for development. Knocking down expression of the transcription factor ZBED1 results in both increased apoptosis, and increased expression of several genes including RELT, in a choriocarcinoma cell line induced to differentiate into trophoblasts [60]. These results indirectly imply a role for RELT in promoting apoptosis in both trophoblasts as well as cancer, as the BeWo cell line used in this study is a carcinoma cell line.…”

“…The cells were sorted into cells undergoing apoptosis versus oncosis, and RELT protein was exclusively associated with the apoptotic population, suggesting that RELT may participate in the induction of apoptosis of acinar cells in pancreatitis. RELT has also been indirectly implicated in the apoptosis of trophoblast cells, as deletion of the transcription factor ZBED1 resulted in both upregulation of RELT mRNA expression and apoptosis of trophoblasts [60]. RELT mRNA expression was downregulated in chicken splenic lymphocytes treated with the protective saponin Rg1 prior to treatment with hydrogen peroxide versus hydrogen peroxide alone, as determined by both transcriptome analysis and qRT-PCR [61].…”