Genome-wide CRISPR-Cas9 knockout screen identifies essential genes and pathways for HLA-G expression in extravillous trophoblast 4327

Abstract Description Maternal-fetal immune tolerance is key to a successful pregnancy. HLA-G, a unique human leukocyte antigen (HLA) molecule found in extravillous trophoblasts (EVT), plays a crucial role in this process by interacting with receptors on maternal immune cells in the uterus. While we know that certain cis-regulatory elements control HLA-G expression, the factors that determine its expression in EVT are not well understood. Through a genome-wide CRISPR-Cas9 knockout (KO) screen, we discovered that the WNT signaling pathway suppresses HLA-G expression in EVT. We also identified two transcription factors, TEAD1 and TEAD3, that are essential for HLA-G transcription in EVT, acting independently of the Yes-associated protein (YAP). In summary, our study sheds light on the key genes and pathways that control HLA-G expression in EVT, helping to better understand the mechanisms of maternal-fetal immune tolerance. This research could also have broader implications for controlling HLA-G expression in other contexts, such as protecting allogenic cells from immune rejection in cell therapies. Funding Sources R01AI145862 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)