Reconstructing the emergence of the human chorion via Hippo-mediated trophoblast induction.

In a developmentally informed human chorion model, LATS kinase inhibition drives ordered trophectoderm-to-secondary chorionic progression, and CLDN6+ ITGA6+ cells mark a proEVT-like intermediate.

• Why it matters: The field lacks a mechanistic, human-specific account of how trophectoderm specification advances to chorion formation, despite known roles for Hippo-LATS-YAP in early fate decisions.
• What they did: The authors used stage-matched single-cell reference mapping after LATS inhibition without exogenous morphogens, then profiled methylation by whole-genome bisulfite sequencing and built a 3D chorion system by agitating induced-cell aggregates in suspension.
• The result: They found naive-like hypomethylation followed by remethylation with placenta-associated imprinted domains retaining methylation and allelic bias; endogenous WNT was dispensable for initial induction but later balanced chorionic lineages, and CLDN6+ ITGA6+ cells showed villous and extravillous potential.

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