A genome-wide CRISPR-Cas9 knockout screen identifies essential and growth-restricting genes in human trophoblast stem cells

• DOI: 10.1038/s41467-022-30207-9
• Publication Date: 2022-05-10T10:03:22Z
• Authors: Chen Dong; Shuhua Fu; Rowan M. Karvas; Brian Chew; Laura A. Fischer; Xiaoyun Xing; Jessica K. Harrison; Pooja Popli; Ramakrishna Komma...; Ting Wang; Bo Zhang; Thorold W. Theuni...
• Keywords: Trophoblast

The recent derivation of human trophoblast stem cells (hTSCs) provides a scalable in vitro model system placental development, but the molecular regulators hTSC identity have not been systematically explored thus far. Here, we utilize genome-wide CRISPR-Cas9 knockout screen to comprehensively identify essential and growth-restricting genes hTSCs. By cross-referencing our data those from similar genetic screens performed other cell types, as well gene expression early embryos, define hTSC-specific -enriched regulators. These include both well-established previously uncharacterized regulators, such ARID3A, GATA2, TEAD1 (essential), GCM1, PTPN14, TET2 (growth-restricting). Integrated analysis chromatin accessibility, expression, location reveals that transcription factor regulates many In absence TEAD1, hTSCs fail complete faithful differentiation into extravillous (EVT) instead show bias towards syncytiotrophoblast (STB) differentiation, indicating this safeguards bipotent lineage potential Overall, study valuable resource for dissecting regulation development diseases.