1. Single-cell assessment of primary and stem cell-derived human trophoblast organoids as placenta-modeling platforms.
- Author
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Shannon MJ, McNeill GL, Koksal B, Baltayeva J, Wächter J, Castellana B, Peñaherrera MS, Robinson WP, Leung PCK, and Beristain AG
- Subjects
- Pregnancy, Female, Humans, Placentation, Stem Cells, Cell Differentiation, Organoids metabolism, Placenta metabolism, Trophoblasts
- Abstract
Human trophoblast stem cells (hTSCs) and related trophoblast organoids are state-of-the-art culture systems that facilitate the study of trophoblast development and human placentation. Using single-cell transcriptomics, we evaluate how organoids derived from freshly isolated first-trimester trophoblasts or from established hTSC cell lines reproduce developmental cell trajectories and transcriptional regulatory processes defined in vivo. Although organoids from primary trophoblasts and hTSCs overall model trophoblast differentiation with accuracy, specific features related to trophoblast composition, trophoblast differentiation, and transcriptional drivers of trophoblast development show levels of misalignment. This is best illustrated by the identification of an expanded progenitor state in stem cell-derived organoids that is nearly absent in vivo and transcriptionally shares both villous cytotrophoblast and extravillous trophoblast characteristics. Together, this work provides a comprehensive resource that identifies strengths and limitations of current trophoblast organoid platforms., Competing Interests: Declaration of interests The authors declare that no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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