VGLL1 regulates extraembryonic lineage specification in human [CUT&TAG]

Placenta abnormality is one of the key reasons for early pregnancy loss but the regulatory mechanisms underlying placenta formation are largely unknown. Here, we applied a human naïve pluripotent stem cell (PSC) derived TE model to explore the driven regulatory machinery. We demonstrate that VGLL1 (vestigial like family member 1) is crucial for TE self-renewal and TE-specific gene expression, thus suppressing VGLL1 leads to severely impaired cell proliferation and skewed TE induction. VGLL1 exerts its function through interacting with TEAD4 (TEA domain transcription factor 4) and colocalize at target gene promoters and enhancers. Further investigation uncovers the enrichment of H3K27ac active histone marks at genomic regions occupied by VGLL1-TEAD4 complex, indicates a close association between them. Overall, our data reveals the critical function model of VGLL1-TEAD4 in human TE derivation, highlighting a potential interspecies difference between human and mouse TE induction. Overall design: Human naïve PSC were plated at a density of 100000 cells per well onextracellular matrix (ECM; Geltrex™)-coated 6-well plates and cultured with TE medium. Cells were collected for sequencing on day 5. For human TSC cells, cells cultured in TS-1 medium for five or six days were plated on Collagen IV coated 6-well plates and cultured with TSC medium. Cells cultured in TSC medium became morphologically stable after 2-3 passages.