A genome-wide CRISPR-Cas9 screen in human trophoblast stem cells

Our study describing a genome-wide CRISPR-Cas9 knockout screen for essential and growth-restricting genes in human trophoblast stem cells (hTSCs) was published in Nature Communications today. By cross-referencing our results to those from similar genetic screens performed in other cell types, as well as gene expression data from early human embryos, we define hTSC-specific and -enriched regulators. These include both well-established and previously uncharacterized trophoblast regulators. Integrated analysis of chromatin accessibility, gene expression, and genome-wide location data reveals that the hTSC-specific essential transcription factor TEAD1 regulates the expression of many trophoblast regulators in hTSCs. In the absence of TEAD1, hTSCs fail to complete faithful differentiation into extravillous trophoblast (EVT) cells and instead show a bias towards syncytiotrophoblast (STB) differentiation. Overall, our study provides a valuable resource for dissecting the molecular regulation of human placental development and pregnancy-related diseases. Congratulations to Chen Dong, who spearheaded this project in collaboration with Shuhua Fu in Bo Zhang’s lab at WashU, and all other contributors!