Three-dimensional molecular architecture of mouse organogenesis

Mammalian embryos exhibits sophisticated cell organizations that are intricately orchestrated at both molecular and cellular level. It has recently become apparent that cells within the animal body display significant heterogeneity, both in terms of their cellular properties and their spatial distributions. However, current spatial transcriptomics profiling either lack three-dimensional representation or are limited in their ability to capture the complexity of embryonic tissues and organs. Here, we present a represented spatial transcriptome atlas of all major organs at embryonic day 13.5 (E13.5) in the mouse embryo, and provide a three- dimensional rendering of molecular regulation for embryonic patterning with stacked sections. By integrating this spatial transcriptome data with corresponding single-cell transcriptome data, we offer a detailed molecular annotation of the dynamic nature of organ development, spatial cellular interaction, embryonic axes and divergence of cell fates underlying mammalian development, which would pave the way for precise organ engineering and stem cell-based regenerative medicine. Overall design: Organogenesis stage (embryonic day 13.5, E13.5) embryos were collected of C57BL/6 mice, and embryos images were taken for recording and conformation of developmental staging. Collected embryos were embedded in Tissue freezing medium and stored at -80°C until sectioning. The whole embryo tissue was serially cryo-sectioned along craniocaudal axis at 10µm, and about 1000 sections were harvested. Considering the morphology and uniform sampling, 10 sections from a male embryo and 4 sections from a female embryo were selected for spatial transcriptomic analysis by 10x Genomics Visium platform.