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A temporally resolved BMP4 response in the peri-implantation human embryonic disc is critical for the induction of multipotent TFAP2A + cells and EMT

ABSTRACT: The unilaminar embryonic disc, a sheet of epithelized SOX2+ epiblast cells, undergoes complex morphogenesis to create a multi-dimensional human gastrula. This process endows early lineage specification and spatial identities that begin at the posterior end of the disc to create a coordinate system for embryogenesis. Here, we find that simply adding basement membrane extracts (BMEs) to the stem cell media is sufficient to model the early peri-gastrulating embryonic disc. We demonstrate that the emergence of amnion, primordial germ cells (PGCs), and mesoderm arise from BMP4-responsive disc cells that induce transient TFAP2A expression and SOX2 repression. We track the order of embryonic events that take place during disc morphogenesis and show that amnion-like cells (AMLCs) and PGC-like cells (PGCLCs) are specified first from epithelized TFAP2A+ progenitors. Shortly after, gastrulating mesoderm-like cells (MeLCs) arise from transiently expressed TFAP2A+ disc cells that then undergo EMT. We find that BMP4-responsiveness is critical to SOX2 repression, TFAP2A expression, lineage induction and EMT, while the process of EMT itself is not. Thus, we show that the extracellular matrix is necessary to promote disc morphogenesis and EMT.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288389 | GEO | 2025/07/30

REPOSITORIES: GEO

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