Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

Abstract

As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.

Identification of Intercellular Crosstalk between Decidual Cells and Niche Cells in Mice

“…Here, we found five stromal cell clusters for the IS (S2, S1, S1p, S3 and S3p) and three stromal cell clusters for the IIS (S2, S1 and S1p). S2 was superficial stromal cells and S1/S1p was deep stromal cells, which is in line with our previous study [ 33 ]. S3 and S3p were IS-specific: S3 was decidual cells expressing the decidualization marker genes Wnt4, Bmp2 and Prl8a2, while S3p was intermediate decidual cells expressing the proliferation marker gene Mki67.…”

“…We have recently established a single-cell atlas of mouse uterus during embryo implantation using the 10× Genomics approach [ 33 ]. In this study, we systematically characterized the mouse uterus on GD8 at a single-cell resolution.…”

Revisiting the Transcriptome Landscape of Pig Embryo Implantation Site at Single-Cell Resolution

“…Vascular endothelial cells had 2 clusters, VE (PECAM1 + VWF + MKI67 - ) and a proliferating subset VEp (PECAM1 + VWF + MKI67 + ). There were 6 immune cell clusters including natural killer cells (NK, PTPRC + CD3E + ), proliferating natural killer cells (NKp, PTPRC + CD3E + MKI67 + ), macrophages (M, PTPRC + CD68 + ), proliferating macrophages (M, PTPRC + CD68 + MKI67 + ), B cells (B, PTPRC + CD79B + ) and proliferating B cells (M, PTPRC + CD79B + MKI67 + ) ( Yang et al, 2021a ; He et al, 2021 ). Finally, we aimed to discover novel markers for each cell type.…”

“…Single-cell dissociation was performed as described previously ( Yang et al, 2021a ; He et al, 2021 ). Endometrial tissues and conceptus fragments from 3 gilts for each group were minced with a blade and then incubated in dissociation buffer containing 2 mg/ml Collagenase II (#C6885, Sigma-Aldrich), 10 mg/ml Dispase II (#354235, Corning) and 50,000 U/ml DNase I (#DN25, Sigma-Aldrich) for up to 30 min at 37°C in a shaking incubator.…”

“…Raw data of fastq files were aligned to the Sscrofa11.1 pig reference genome by using the CellRanger software v3.0.1 (10x Genomics). The resulting gene counts matrix was processed with a computational pipeline as described previously ( Yang et al, 2021a ; He et al, 2021 ). Briefly, cells with <200 or >6000 unique genes, as well as cells with >25% of mitochondrial counts, were discarded.…”