Single-cell assessment of primary and stem cell-derived human trophoblast organoids as placenta-modeling platforms

The research explores the efficacy of human trophoblast stem cells (hTSCs) and associated trophoblast organoids as advanced culture systems for investigating trophoblast development and placentation in humans. Through single-cell transcriptomics, the study assesses how organoids, derived from freshly isolated first-trimester trophoblasts or established hTSC cell lines, replicate developmental cell trajectories and transcriptional regulatory processes observed in vivo. While both primary trophoblast-derived organoids and hTSC-derived organoids generally replicate trophoblast differentiation accurately, discrepancies exist in specific aspects such as trophoblast composition, differentiation, and transcriptional regulation. Notably, hTSC-derived organoids exhibit an expanded progenitor state not prominent in vivo, demonstrating characteristics of both villous cytotrophoblasts and extravillous trophoblasts. This research serves as a comprehensive assessment, outlining the strengths and limitations of current trophoblast organoid platforms.