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!

Paper on stem-cell-derived trophoblast organoids

Our paper on stem-cell-derived trophoblast organoids (SC-TOs) was published in Cell Stem Cell today. In this work we describe a methodology for deriving self-renewing 3D trophoblast organoids from naive human pluripotent stem cells (hPSCs). Using single cell transcriptome analysis, we demonstrate that these organoids contain diverse trophoblast progenitor and specialized cell types that closely correspond to trophoblast identities in the post-implantation embryo. These organoid cultures also model placental X inactivation dynamics and selective vulnerability to emerging pathogens (SARS-CoV-2 and Zika virus). Big congrats to all members of the team, especially Rowan Karvas, and our collaborators Indira Mysorekar, Sabine Dietmann, Jacco Boon, and Liang Ma!

Chen Dong defends PhD thesis

Chen Dong successfully defended his PhD thesis, entitled “Investigating the specification and regulation of the human trophoblast lineage using cell culture models” on Friday, April 29th, 2022. Chen pioneered our efforts to derive human trophoblast stem cells (hTSCs) from naive pluripotent stem cells and performed a genome-wide CRISPR screen that identified essential and growth-restricting genes in hTSCs. He’s also the first PhD student to graduate from the Theunissen Lab. Congratulations Dr. Dong!