Primary specification of blastocyst trophectoderm by scRNA-seq: new insights into embryo implantation. Primary specification of blastocyst trophectoderm by scRNA-seq: new insights into embryo implantation

Mechanisms of implantation such as determination of the attachment pole, fetal-maternal communication, as well as underlying causes of implantation failure are largely unexplored. Here we performed single-cell RNA sequencing (scRNA-seq) on peri-implantation embryos from both humans and mice to explore trophectoderm development and embryo–endometrium crosstalk. We found that the transcriptomes of polar and mural trophectoderm (TE) diverged after embryos hatched from the zona pellucida in both species, with polar TE being more mature than mural TE. The implantation poles show similarities in cell cycle activities, as well as in expression of genes critical for implantation and placentation. Embryos that either fail to attach in vitro or fail to implant in vivo, show abnormalities in pathways related to energy production, protein metabolism and 18S rRNA m6A methylation. These findings uncover the gene expression characteristics of humans and mice TE differentiation during the peri-implantation period and provide new insights into embryo implantation. Overall design: Transcriptome of trophectoderm cells from peri-implantation human and mice embryos were analyzed by single cell RNA-seq

胚胎着床的相关机制——如附着极的确定、胎儿-母体间的信号交流，以及着床失败的潜在诱因，目前仍有大量未被探明之处。本研究针对人类与小鼠的围着床期胚胎开展单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），以探究滋养外胚层（trophectoderm, TE）发育以及胚胎-子宫内膜串扰调控机制。
研究发现，在两个物种中，胚胎从透明带（zona pellucida）孵出后，极滋养外胚层与壁滋养外胚层的转录组便出现分化，且极滋养外胚层的成熟度高于壁滋养外胚层。着床极在细胞周期活性以及着床与胎盘形成相关的关键基因表达上均具有相似性。体外无法附着或体内无法着床的胚胎，其能量产生、蛋白质代谢以及18S rRNA m⁶A甲基化相关通路均存在异常。
本研究揭示了人类与小鼠围着床期滋养外胚层分化过程中的基因表达特征，为胚胎着床研究提供了全新视角。
实验设计：通过单细胞RNA测序对人类与小鼠围着床期胚胎的滋养外胚层细胞转录组进行分析。