Single-cell RNA-seq reveals sequential trophoblast transition during human embryo implantation. Single-cell RNA-seq reveals sequential trophoblast transition during human embryo implantation

We performed single-cell RNA sequencing (scRNA-seq) analysis of human post-implantation trophoblast cells. A hierarchical model was established, which was characterized by the sequential and stepwise development of two primitive cytotrophoblast cell (pCTB) subtypes after the trophectoderm (TE), two primitive syncytiotrophoblast (pSTB) subtypes, and migrative trophoblast cells (MTB). Further analysis characterized a new subtype of fusion-competent cells, which not only prepare for fusion to form primitive syncytiotrophoblast but also possess migration ability, which could be dual-function cells during implantation. Our work allows for reconstruction of sequential trophoblast cell transcriptional programs transition during implantation and provides a valuable resource to study pathologies in early pregnancy, such as recurrent implantation failure. Overall design: Combining the in vitro culture of human embryos to the post-implantation stage with scRNA-seq technology, we developed a comprehensive resource characterizing the transcriptional dynamics of trophoblast specification. RNA was extracted from 12 human embryos from day 8 to day 13.

本研究针对人类植入后滋养层细胞开展了单细胞RNA测序（single-cell RNA sequencing，简称scRNA-seq）分析。本研究构建了一套层级化发育模型，该模型刻画了滋养外胚层（trophectoderm，简称TE）分化后，两类原始细胞滋养层细胞（primitive cytotrophoblast cell，简称pCTB）亚型、两类原始合体滋养层细胞（primitive syncytiotrophoblast，简称pSTB）亚型以及迁移性滋养层细胞（migrative trophoblast cells，简称MTB）依次逐步发育的特征。后续进一步分析鉴定出一类全新的融合潜能细胞亚型：该类细胞不仅可介导融合以形成原始合体滋养层细胞，同时还具备迁移能力，属于植入过程中兼具双重功能的细胞类群。本研究可重构植入过程中滋养层细胞转录程序的时序转变过程，同时为早期妊娠相关病理（如复发性植入失败（recurrent implantation failure））的研究提供了宝贵的研究资源库。实验设计概述：本研究将人类胚胎体外培养至植入后阶段的技术与scRNA-seq技术相结合，构建了一套可全面表征滋养层细胞特化过程转录动态变化的研究资源库。本研究共提取了8日龄至13日龄的12枚人类胚胎的总RNA。