biostudies-literatureSiriwardena DWellcome TrustUniversity of Cambridge Centre for Trophoblast Research1427-1446.e8https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616712biostudies-literatureUnknown31(10)Early human trophoblast development has remained elusive due to the inaccessibility of the early conceptus. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Here, we tracked the pre- to postimplantation transition of the trophoblast lineage in superficially implanting marmoset embryos in vivo. We differentiated marmoset naive pluripotent stem cells into trophoblast stem cells (TSCs), which exhibited trophoblast-specific transcriptome, methylome, differentiation potential, and long-term self-renewal. Notably, human TSC culture conditions failed to support marmoset TSC derivation, instead inducing an extraembryonic mesoderm-like fate in marmoset cells. We show that combined MEK, TGF-β/NODAL, and histone deacetylase inCell stem cellMarmoset and human trophoblast stem cells differ in signaling requirements and recapitulate divergent modes of trophoblast invasion.PMC7616712203151/A/16/Z203151/Z/16/Z203151WT108438/C/15/Z206684108438Reik WKohler TNRawlings TMSlatery EEllermann ALLinneberg-Agerholm MClark SJZernicka-Goetz MSiriwardena DWeberling AMunger CHollfelder FBoroviak TESasaki EPenfold CBergmann SBrickman JMBrosens JJBehr RfalseMarmoset and human trophoblast stem cells differ in signaling requirements and recapitulate divergent modes of trophoblast invasion.Early human trophoblast development has remained elusive due to the inaccessibility of the early conceptus. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Here, we tracked the pre- to postimplantation transition of the trophoblast lineage in superficially implanting marmoset embryos in vivo. We differentiated marmoset naive pluripotent stem cells into trophoblast stem cells (TSCs), which exhibited trophoblast-specific transcriptome, methylome, differentiation potential, and long-term self-renewal. Notably, human TSC culture conditions failed to support marmoset TSC derivation, instead inducing an extraembryonic mesoderm-like fate in marmoset cells. We show that combined MEK, TGF-β/NODAL, and histone deacetylase in2024-01-01T00:00:00Z2024 Oct2025-04-04T02:21:13.208Z2025-04-04T02:21:13.208ZS-EPMC76167123932179710.1016/j.stem.2024.09.004