Spatiotemporally resolved transcriptome atlas of developing mouse placenta reveals mechanisms of embryonic lethality

Proper placentation is essential for embryonic growth and viability, yet the spatial organization and interactions of placental cell types remain incompletely understood. Here, we present a spatiotemporal transcriptomic atlas of the mouse placenta (STAMP) from embryonic days 9.5 to 18.5 at single-cell resolution. This atlas delineates major placental cell types and developmental trajectories. We observed labyrinth region expansion through branching morphogenesis, with trophoblast progenitor cells declining and terminally differentiated trophoblast cells increasing from E12.5 onward, and glycogen cells (GCs) transitioned from the junctional zone (JZ) to the maternal decidua. Furthermore, we found two novel GC subclusters with distinct spatial distributions and molecular features. Analysis of defective placentas revealed an increased number of GCs and altered macrophage distribution in the labyrinth layer. Transmission electron microscopy and glycogen content examination confirmed sluggish glycogen breakdown, while macrophage accumulation correlated with tissue remodeling and immune responses. Our spatial transcriptomic analysis elucidates mechanisms underlying placental abnormalities and embryonic lethality. This atlas enhances understanding of mouse placental development, aids in identifying developmental defects and pathogenic causes in dysfunctional placentas, and provides valuable insights for optimizing in vitro embryo culture conditions.