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Abstract

The emergence of the three primary germ layers and the appearance of lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over four hundred thousand cells from 14 human samples collected from postconceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. Using this unique dataset, we describe the diversification of cell types, the spatial patterning of the neural tube cells, and the signaling pathways 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 brain development in humans.

A single-cell atlas of early human embryogenesis

To gain a global perspective of cellular diversification during early human embryogenesis, we collected 14 human samples between PCW 3 and 12, prepared single-cell suspensions, and processed them for scRNA-seq using a droplet-based platform. A total of 430,808 cells were analyzed following quality control processing. We clustered 90 clusters with cells from the three germ layers based on the expression of typical marker genes.