A spatiotemporal transcriptomic atlas of mouse placentation

Abstract The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3 , Jun , Junb , Stat6 , Mxd1 , Maff , Fos , and Irf7 , involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.