Spatial multi-omic atlas profiles early organogenesis of a Carnegie stage 12 human embryo.

Organogenesis marks one of the most dynamic periods of early human embryonic development. Although the morphological features of this period have been described, the underlying transcriptional and metabolic landscapes remain poorly understood owing to the lack of an integrated spatial strategy. We present spatial transcriptomic and metabolomic maps of a Carnegie stage 12 (CS12) human embryo, co-registered with embryonic anatomy to generate a unified spatial multi-omic framework. Unsupervised clustering of the spatial transcriptomic data identified 17 cell populations covering the major organ primordia. Notably, we observed spatially separable hepatocyte- and cholangiocyte-lineage primed transcriptional programmes within the liver primordium, and detected cardiac outflow tract and sinoatrial node progenitors at CS12. Furthermore, integration of gene and metabolite abundance highlighted regional associations between transcription factors and metabolic pathways underpinning lineage specification. Our work presents a spatially resolved multi-omic atlas of a human embryo at the onset of organogenesis.