Spatiotemporal insight into early pregnancy governed by immune-featured stromal cells [RNA-seq]

Endometrial decidualization connecting embryo implantation and placentation is transient, but essential for successful pregnancy, which however is not systematically investigated. Here, by using a novel single-cell spatial transcriptomic profiling technology (scStereo-seq), we were able to visualize and define key and dynamic functional decidual hubs assembled by distinct immune, endothelial, trophoblast and decidual stromal cells (DSCs) during early pregnancy in mice. We classified DSC subclusters and described their transdifferentiation trajectory controlled by transcription factor cascades. Interestingly, we discovered a novel type of DSCs expressing immune cell-specific genes, termed immune DSCs (iDSCs). Whereas immature DSCs attracted immune cells and induced decidual angiogenesis at the mesenchymal-to-epithelial transition (MET) hub during decidualization initiation, iDSCs enabled immune cell recruitment, angiogenesis facilitation and cytotoxic effect induction to form immune cell assembling and angiogenesis hubs, which eventually allow decidual homeostasis maintenance and decidualization-to-placentation transition. We spatiotemporally decode mouse early pregnancy events controlled by immune DSCs. In vitro decidualization was induced from primary endometrialum stromal cells by using progesterone (P4) and cAMP-stimulation. Then, one primary endometrial stromal cells (control) and samples were collected at different time points (Day1-Day5) and subjected to bulk RNA sequencing.