The British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Obstetrics & Gynecology, The University of British Columbia, Vancouver, BC, Canada.
Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
Dev Cell. 2024 Mar 25;59(6):776-792.e11. doi: 10.1016/j.devcel.2024.01.023. Epub 2024 Feb 14.
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.
人滋养层干细胞（hTSC）和相关滋养层类器官是最先进的培养系统，可促进滋养层发育和人胎盘形成的研究。我们使用单细胞转录组学来评估源自新鲜分离的早期滋养层或已建立的 hTSC 细胞系的类器官如何再现体内定义的发育细胞轨迹和转录调控过程。尽管源自原发性滋养层和 hTSC 的类器官总体上能够准确模拟滋养层分化，但与滋养层组成、滋养层分化以及滋养层发育的转录驱动因素相关的特定特征显示出不同程度的不匹配。这一点通过在干细胞衍生的类器官中鉴定出一个扩展的祖细胞状态得到了最好的说明，该状态在体内几乎不存在，并且在转录上同时具有绒毛细胞滋养层和绒毛外滋养层的特征。总之，这项工作提供了一个全面的资源，确定了当前滋养层类器官平台的优势和局限性。
