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

Autor: Shannon MJ; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., McNeill GL; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., Koksal B; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., Baltayeva J; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., Wächter J; Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria., Castellana B; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., Peñaherrera MS; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada., Robinson WP; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada., Leung PCK; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada., Beristain AG; The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada. Electronic address: aberista@mail.ubc.ca.
Jazyk: angličtina
Zdroj: Developmental cell [Dev Cell] 2024 Mar 25; Vol. 59 (6), pp. 776-792.e11. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1016/j.devcel.2024.01.023
Abstrakt: 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.)
Databáze: MEDLINE