The single-cell and spatial transcriptional landscape of human gastrulation and early brain development

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia. We resolved 24 clusters of radial glial cells along the neural tube and outlined differentiation trajectories for the main classes of neurons. Lastly, we identified conserved and distinctive features across species by comparing early embryonic single-cell transcriptomic profiles between humans and mice. This comprehensive atlas sheds light on the molecular mechanisms underlying gastrulation and early human brain development. [Display omitted] •The spatial patterning of neural tube cells during human gastrulation•NE to RG transformation is determined by several essential signaling pathways•RG subtypes exhibit spatial location distribution with distinctive gene expression•Human-specific features are presented during early nervous system development Zeng et al. illustrate the transcriptional profiles and spatial organization of different cell types during human gastrulation and early nervous system development. They reveal the spatial patterning of neural tube cells, molecular programs driving NE to RG transformation, diversity of RG subtypes, and species differences of early nervous system development.